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-Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
-{{TOC limit|limit=3}}
-=Untreated=
-==Alemtuzumab (Campath)==
-===Regimen, Hillmen et al. 2007 (CAM 307)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Alemtuzumab (Campath)]] 3 mg IV once per day, then increased as tolerated in terms of infusion reactions to [[Alemtuzumab (Campath)]] 10 mg IV once per day, and then to [[Alemtuzumab (Campath)]] 30 mg IV once per day.  Once 30 mg dose is tolerated, administer [[Alemtuzumab (Campath)]] 30 mg IV over 2 hours, 3 times per week
-Supportive medications (see references for details, as they differ by paper):
-*[[Diphenhydramine (Benadryl)]] 50 mg PO once 30 minutes prior to [[Alemtuzumab (Campath)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Alemtuzumab (Campath)]]
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO 3 times per week, starting on day 8, continuing at a minimum until 2 months after treatment is complete
-*[[Famciclovir (Famvir)]] 250 mg PO BID, starting on day 8, continuing at a minimum until 2 months after treatment is complete
-'''up to 12 to 16 weeks of therapy;''' total course varies depending on reference
-===References===
-# Hillmen P, Skotnicki AB, Robak T, Jaksic B, Dmoszynska A, Wu J, Sirard C, Mayer J. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007 Dec 10;25(35):5616-23. Epub 2007 Nov 5. [http://jco.ascopubs.org/content/25/35/5616.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17984186 PubMed]
-==Bendamustine (Treanda)==
-===Regimen, Knauf et al. 2009===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Bendamustine (Treanda)]] 100 mg/m2 IV over 30 minutes once per day on days 1 & 2
-'''28-day cycles x 6 cycles;''' Niederle et al. 2013 treated patients for up to 8 cycles
-===References===
-# Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Tremmel L, Merkle K, Montillo M. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009 Sep 10;27(26):4378-84. Epub 2009 Aug 3. [http://jco.ascopubs.org/content/27/26/4378.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19652068 PubMed]
-# '''Update:''' Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Merkle K, Montillo M. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012 Oct;159(1):67-77. Epub 2012 Aug 4. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12000/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22861163 PubMed]
-# '''Retrospective:''' Kolibaba KS, Sterchele JA, Joshi AD, Forsyth M, Alwon E, Beygi H, Kennealey GT. Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study. Ther Adv Hematol. 2013 Jun;4(3):157-71. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666446/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23730494 PubMed]
-==BR==
-BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
-===Regimen, Eichhorst et al. 2013 (GCLLSG CLL10)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Bendamustine (Treanda)]] 90 mg/m2 IV once per day on days 1 & 2
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 0 of the first cycle, then 500 mg/m2 IV once on day 1 on cycle 2 and subsequent cycles
-'''28-day cycles x up to 6 cycles based on response and toxicity'''
-===References===
-# Fischer K, Cramer P, Busch R, Böttcher S, Bahlo J, Schubert J, Pflüger KH, Schott S, Goede V, Isfort S, von Tresckow J, Fink AM, Bühler A, Winkler D, Kreuzer KA, Staib P, Ritgen M, Kneba M, Döhner H, Eichhorst BF, Hallek M, Stilgenbauer S, Wendtner CM. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2012 Sep 10;30(26):3209-16. Epub 2012 Aug 6. [http://jco.ascopubs.org/content/30/26/3209.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22869884 PubMed]
-# '''Retrospective:''' Kolibaba KS, Sterchele JA, Joshi AD, Forsyth M, Alwon E, Beygi H, Kennealey GT. Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study. Ther Adv Hematol. 2013 Jun;4(3):157-71. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666446/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23730494 PubMed]
-# Barbara Eichhorst, MD, Anna-Maria Fink, MD, Raymonde Busch, PhD, Elisabeth Lange, MD, Hubert Köppler, Prof. Dr., Michael Kiehl, MD, Martin Sökler, MD, Rudolf Schlag, MD, Ursula Vehling-Kaiser, MD, Georg Köchling, MD, Christoph Plöger, MD, Michael Gregor, MD, Torben Plesner, MD, Marek Trneny, MD, Ph.D., Prof, Kirsten Fischer, MD, Hartmut Döhner, MD, Michael Kneba, MD, Clemens Wendtner, MD, Wolfram Klapper, Karl-Anton Kreuzer, Dr. med., Stephan Stilgenbauer, MD, Sebastian Böttcher, MD, and Michael Hallek, MD. Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG). 2013 ASH Annual Symposium abstract 526 [http://bloodjournal.hematologylibrary.org/content/122/21/526 link to abstract]
-==CAP==
-CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin, '''<u>P</u>'''rednisone
-===Regimen #1, Leporrier et al. 2001===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
-*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
-'''Monthly cycles x 6 cycles'''
-===References===
-# Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C; French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001 Oct 15;98(8):2319-25. [http://bloodjournal.hematologylibrary.org/content/98/8/2319.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11588025 PubMed]
-==CC==
-CC: '''<u>C</u>'''ladribine, '''<u>C</u>'''yclophosphamide
-===Regimen, Robak et al. 2010 (PALG-CLL3)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 30 minutes once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 3
-Supportive medications:
-*"No routine prophylaxis with antibiotics, antiviral agents, or growth factors."
-'''28-day cycles x up to 6 cycles'''
-===References===
-# Robak T, Jamroziak K, Gora-Tybor J, Stella-Holowiecka B, Konopka L, Ceglarek B, Warzocha K, Seferynska I, Piszcz J, Calbecka M, Kostyra A, Dwilewicz-Trojaczek J, Dmoszyñska A, Zawilska K, Hellmann A, Zdunczyk A, Potoczek S, Piotrowska M, Lewandowski K, Blonski JZ. Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study). J Clin Oncol. 2010 Apr 10;28(11):1863-9. Epub 2010 Mar 8. [http://jco.ascopubs.org/content/28/11/1863.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20212251 PubMed]
-==Chlorambucil (Leukeran)==
-===Regimen #1, Catovsky et al. 2007 (LRF CLL4)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 10 mg/m2 PO once per day on days 1 to 7
-Supportive medications:
-*Patients with stage C disease (hemoglobin <10 g/dL or platelet count <100 x 10^9/L) received [[Prednisolone (Millipred)]] 30 mg/m2 PO once per day x 3 weeks, then 1 week taper before starting [[Chlorambucil (Leukeran)]] to reduce its myelotoxicity
-'''28-day cycles x up to 12 cycles'''
-===Regimen #2, Dighiero et al. 1998===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 0.1 mg/kg PO once per day
-'''continue until progression'''
-===Regimen #3, Rai et al. 2000 (CALGB 9011) & Hillmen et al. 2007 (CAM 307)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 40 mg/m2 PO once on day 1
-'''28-day cycles x up to 12 cycles'''
-===Regimen #4, Knauf et al. 2009===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 0.8 mg/kg PO once per day on days 1 & 15
-**Alternate schedule, "divided doses on days 1 to 2 and 15 to 16 for patient comfort in some individual cases": [[Chlorambucil (Leukeran)]] 0.4 mg/kg PO once per day on days 1 to 2, 15 to 16
-'''28-day cycles x up to 6 cycles'''
-===Regimen #5, Eichhorst et al. 2009 (GCLLSG CLL5)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 0.4 mg/kg PO once on day 1, to be increased as tolerated by 0.1 mg/kg each cycle, up to a maximum of [[Chlorambucil (Leukeran)]] 0.8 mg/kg PO once on day 1
-'''14-day cycles x up to 24 cycles'''
-===Regimen #6, Goede et al. 2013 (CLL11/BO21004)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 0.5 mg/kg PO once per day on days 1 & 15
-'''28-day cycles x 6 cycles'''
-===References===
-# Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet JL, Travade P. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med. 1998 May 21;338(21):1506-14. [http://www.nejm.org/doi/full/10.1056/NEJM199805213382104#t=article link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9593789 PubMed]
-# Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [http://www.nejm.org/doi/full/10.1056/NEJM200012143432402 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11114313 PubMed]
-# Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2961125-8/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17658394 PubMed]
-# Hillmen P, Skotnicki AB, Robak T, Jaksic B, Dmoszynska A, Wu J, Sirard C, Mayer J. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007 Dec 10;25(35):5616-23. Epub 2007 Nov 5. [http://jco.ascopubs.org/content/25/35/5616.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17984186 PubMed]
-# Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Tremmel L, Merkle K, Montillo M. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009 Sep 10;27(26):4378-84. Epub 2009 Aug 3. [http://jco.ascopubs.org/content/27/26/4378.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19652068 PubMed]
-# Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhöfer N, Rohrberg R, Söling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Döhner H, Emmerich B, Hallek M; German CLL Study Group (GCLLSG). First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15;114(16):3382-91. Epub 2009 Jul 15. [http://bloodjournal.hematologylibrary.org/content/114/16/3382.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19605849 PubMed]
-# '''Update:''' Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Merkle K, Montillo M. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012 Oct;159(1):67-77. Epub 2012 Aug 4. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12000/full link to original article]  '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22861163 PubMed]
-# '''Abstract:''' Valentin Goede, Kirsten Fischer, Kathryn Humphrey, Elina Asikanius, Raymonde Busch, Anja Engelke, Clemens M. Wendtner, Olga Samoylova, Tatiana Chagorova, Marie-Sarah Dilhuydy, Javier De La Serna Torroba, Thomas Illmer, Stephen Opat, Carolyn Owen, Karl A Kreuzer, Anton W Langerak, Matthias Ritgen, Stephan Stilgenbauer, Michael Wenger, Michael Hallek; German CLL Study Group. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial. J Clin Oncol 31, 2013 (suppl; abstr 7004) [http://meetinglibrary.asco.org/content/116249-132 link to abstract]
-# Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions. N Engl J Med. 2014 Jan 8. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1313984 link to original article]  '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24401022 PubMed]
-==Chlorambucil & Obinutuzumab (GClb)==
-GClb: '''<u>G</u>'''A101 (obinutuzumab), '''<u>C</u>'''h'''<u>l</u>'''oram'''<u>b</u>'''ucil
-===Regimen, Goede et al. 2013 (CLL11/BO21004)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Obinutuzumab (Gazyva)]] 100 mg IV once on cycle 1 day 1; then [[Obinutuzumab (Gazyva)]] 900 mg IV once on cycle 1 day 2; then [[Obinutuzumab (Gazyva)]] 1000 mg IV once per day on days 8 & 15 of cycle 1; then [[Obinutuzumab (Gazyva)]] 1000 mg IV once on day 1 of subsequent cycles
-*[[Chlorambucil (Leukeran)]] 0.5 mg/kg PO once on days 1 & 15
-'''28-day cycles x 6 cycles'''
-===References===
-# '''Abstract:''' Valentin Goede, Kirsten Fischer, Kathryn Humphrey, Elina Asikanius, Raymonde Busch, Anja Engelke, Clemens M. Wendtner, Olga Samoylova, Tatiana Chagorova, Marie-Sarah Dilhuydy, Javier De La Serna Torroba, Thomas Illmer, Stephen Opat, Carolyn Owen, Karl A Kreuzer, Anton W Langerak, Matthias Ritgen, Stephan Stilgenbauer, Michael Wenger, Michael Hallek; German CLL Study Group. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial. J Clin Oncol 31, 2013 (suppl; abstr 7004) [http://meetinglibrary.asco.org/content/116249-132 link to abstract]
-# Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions. N Engl J Med. 2014 Jan 8. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1313984 link to original article]  '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24401022 PubMed]
-==Chlorambucil & Prednisone==
-===Regimen #1, Raphael et al. 1991===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 30 mg/m2 PO once on day 1
-*[[Prednisone (Sterapred)]] 80 mg PO once per day on days 1 to 5
-'''14-day cycles x up to 18 months'''
-===Regimen #2, Dighiero et al. 1998===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 0.3 mg/kg PO once per day on days 1 to 5
-*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
-'''1-month cycles x up to 36 months'''
-===References===
-# Raphael B, Andersen JW, Silber R, Oken M, Moore D, Bennett J, Bonner H, Hahn R, Knospe WH, Mazza J et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol. 1991 May;9(5):770-6. [http://jco.ascopubs.org/content/9/5/770.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/2016618 PubMed]
-# Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet JL, Travade P. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med. 1998 May 21;338(21):1506-14. [http://www.nejm.org/doi/full/10.1056/NEJM199805213382104#t=article link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9593789 PubMed]
-==Chlorambucil & Rituximab (RClb)==
-RClb: '''<u>R</u>'''ituximab, '''<u>C</u>'''h'''<u>l</u>'''oram'''<u>b</u>'''ucil
-===Regimen #1, Goede et al. 2013 (CLL11/BO21004)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Chlorambucil (Leukeran)]] 0.5 mg/kg PO once per day on days 1 & 15
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on cycle 1 day 1; then [[Rituximab (Rituxan)]] 500 mg/m2 IV once on day 1 of subsequent cycles
-'''28-day cycles x 6 cycles'''
-===Regimen #2, Hillmen et al. 2014 (NCRI CLL208)===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Chlorambucil (Leukeran)]] 10 mg/m2 PO once per day on days 1 & 7
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on cycle 1 day 1; then [[Rituximab (Rituxan)]] 500 mg/m2 IV once on day 1 of subsequent cycles
-'''28-day cycles x 6 cycles; patients not achieving CR could have up to 6 more cycles of chlorambucil alone'''
-===References===
-# '''Abstract:''' Valentin Goede, Kirsten Fischer, Kathryn Humphrey, Elina Asikanius, Raymonde Busch, Anja Engelke, Clemens M. Wendtner, Olga Samoylova, Tatiana Chagorova, Marie-Sarah Dilhuydy, Javier De La Serna Torroba, Thomas Illmer, Stephen Opat, Carolyn Owen, Karl A Kreuzer, Anton W Langerak, Matthias Ritgen, Stephan Stilgenbauer, Michael Wenger, Michael Hallek; German CLL Study Group. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial. J Clin Oncol 31, 2013 (suppl; abstr 7004) [http://meetinglibrary.asco.org/content/116249-132 link to abstract]
-# Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions. N Engl J Med. 2014 Jan 8. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1313984 link to original article]  '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24401022 PubMed]
-# Hillmen P, Gribben JG, Follows GA, Milligan D, Sayala HA, Moreton P, Oscier DG, Dearden CE, Kennedy DB, Pettitt AR, Nathwani A, Varghese A, Cohen D, Rawstron A, Oertel S, Pocock CF. Rituximab Plus Chlorambucil As First-Line Treatment for Chronic Lymphocytic Leukemia: Final Analysis of an Open-Label Phase II Study. J Clin Oncol. 2014 Mar 17. [Epub ahead of print] [http://jco.ascopubs.org/content/32/12/1236.full link to original article]  '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24638012 PubMed]
-==CHOP==
-CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
-===Regimen===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 PO once per day on days 1 to 5
-*[[Doxorubicin (Adriamycin)]] 25 mg/m2 IV once on day 1
-*[[Vincristine (Oncovin)]] 1 mg/m2 IV once on day 1
-*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
-'''28-day cycles x 6 cycles'''
-===References===
-# Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C; French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001 Oct 15;98(8):2319-25. [http://bloodjournal.hematologylibrary.org/content/98/8/2319.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11588025 PubMed]
-==Cladribine (Leustatin)==
-===Regimen, Saven et al. 1995===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Cladribine (Leustatin)]] 0.1 mg/m2/day IV continuous infusion on days 1 to 7 (total dose per cycle: 0.7 mg/m2)
-'''28 to 35-day cycles, repeated until maximum response or limiting toxicity'''
-===References===
-# Saven A, Lemon RH, Kosty M, Beutler E, Piro LD. 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. J Clin Oncol. 1995 Mar;13(3):570-4. [http://jco.ascopubs.org/content/13/3/570.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7884417 PubMed]
-==CVP==
-CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
-===Regimen #1, Raphael et al. 1991===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 PO once per day on days 1 to 5
-*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV once on day 1
-*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
-'''21-day cycles x up to 18 months'''
-===Regimen #2, Hochster et al. 2009 (ECOG1496)
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m2 IV once on day 1
-*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
-*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
-'''21-day cycles x 6 to 8 cycles'''
-''Patients were then randomized to maintenance [[Rituximab (Rituxan)]] or observation.''
-===References===
-# Raphael B, Andersen JW, Silber R, Oken M, Moore D, Bennett J, Bonner H, Hahn R, Knospe WH, Mazza J et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol. 1991 May;9(5):770-6. [http://jco.ascopubs.org/content/9/5/770.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/2016618 PubMed]
-# Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
-==FC==
-FC: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide
-===Regimen #1, Catovsky et al. 2007 (LRF CLL4); Robak et al. 2010 (PALG-CLL3); Hallek et al. 2010 (GCLLSG CLL8)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 3
-Supportive medications (per Robak et al. 2010):
-*"No routine prophylaxis with antibiotics, antiviral agents, or growth factors."
-'''28-day cycles x up to 6 cycles'''
-===Regimen #2, Eichhorst et al. 2006 (GCLLSG CLL4)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 30 mg/m2 IV over 30 minutes once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV over 30 minutes once per day on days 1 to 3
-Supportive medications:
-*No routine antibiotic, antiviral, or growth factor use
-'''28-day cycles x up to 6 cycles'''
-===Regimen #3, Flinn et al. 2007 (ECOG E2997)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 20 mg/m2 IV once per day on days 1 to 5
-*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
-'''28-day cycles x up to 6 cycles'''
-===Regimen #4, Catovsky et al. 2007 (LRF CLL4 PO regimen)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 24 mg/m2 PO once per day on days 1 to 5
-*[[Cyclophosphamide (Cytoxan)]] 150 mg/m2 PO once per day on days 1 to 5
-'''28-day cycles x up to 6 cycles'''
-===References===
-# Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jäger U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Döhner H, Brittinger G, Emmerich B, Hallek M; German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006 Feb 1;107(3):885-91. Epub 2005 Oct 11. [http://bloodjournal.hematologylibrary.org/content/107/3/885.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16219797 PubMed]
-# Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, Hussein MA, Appelbaum FR, Larson RA, Moore DF Jr, Tallman MS. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007 Mar 1;25(7):793-8. Epub 2007 Feb 5. [http://jco.ascopubs.org/content/25/7/793.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17283364 PubMed]
-# Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2961125-8/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17658394 PubMed]
-# Robak T, Jamroziak K, Gora-Tybor J, Stella-Holowiecka B, Konopka L, Ceglarek B, Warzocha K, Seferynska I, Piszcz J, Calbecka M, Kostyra A, Dwilewicz-Trojaczek J, Dmoszyñska A, Zawilska K, Hellmann A, Zdunczyk A, Potoczek S, Piotrowska M, Lewandowski K, Blonski JZ. Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study). J Clin Oncol. 2010 Apr 10;28(11):1863-9. Epub 2010 Mar 8. [http://jco.ascopubs.org/content/28/11/1863.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20212251 PubMed]
-# Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2;376(9747):1164-74. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961381-5/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20888994 PubMed]
-==FCR==
-FCR: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
-===Regimen #1, Tam et al. 2006===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV over 15 to 30 minutes once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV over 15 to 30 minutes once per day on days 1 to 3
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
-'''28-day cycles x up to 6 cycles or "attainment of maximum response"'''
-===Regimen #2, Keating et al. 2005; Tam et al. 2008===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 1 to 3
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 of cycle 1; then 500 mg/m2 IV once on day 1 of cycles 2 to 6
-Supportive medications (varied according to reference):
-*[[Diphenhydramine (Benadryl)]] 25 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 7 of cycle 1
-*Some patients received:
-**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO two times per week
-**[[Valacyclovir (Valtrex)]] 500 mg once per day
-'''28-day cycles x 6 cycles'''
-===Regimen #3, Hallek et al. 2010 (GCLLSG CLL8); Eichhorst et al. 2013 (GCLLSG CLL10)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 1 to 3
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 0 of cycle 1; then 500 mg/m2 IV once on day 1 of cycles 2 to 6
-Supportive medications:
-*PCP (Pneumocystis jirovecii pneumonia) prophylaxis recommended for severe leukopenia >7 days
-*No routine prophylaxis with antiviral medications or G-CSF
-'''28-day cycles x 6 cycles'''
-===References===
-# Keating MJ, O'Brien S, Albitar M, Lerner S, Plunkett W, Giles F, Andreeff M, Cortes J, Faderl S, Thomas D, Koller C, Wierda W, Detry MA, Lynn A, Kantarjian H. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 20;23(18):4079-88. Epub 2005 Mar 14. [http://jco.ascopubs.org/content/23/18/4079.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15767648 PubMed]
-# Tam CS, Wolf M, Prince HM, Januszewicz EH, Westerman D, Lin KI, Carney D, Seymour JF. Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma. Cancer. 2006 Jun 1;106(11):2412-20. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21882/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16649223 PubMed]
-# '''Update:''' Tam CS, O'Brien S, Wierda W, Kantarjian H, Wen S, Do KA, Thomas DA, Cortes J, Lerner S, Keating MJ. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008 Aug 15;112(4):975-80. Epub 2008 Apr 14. [http://bloodjournal.hematologylibrary.org/content/112/4/975.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18411418 PubMed]
-# Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2;376(9747):1164-74. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961381-5/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20888994 PubMed]
-# Carmen D Schweighofer, MD, Florence Cymbalista, MD, Carolin Müller, MD, Raymonde Busch, PhD, Raphael Porcher, PhD, Petra Langerbeins, MD, Bruno Cazin, MD, Anna-Maria Fink, MD, Brigitte Dreyfus, MD, Stefan Ibach, Stéphane Leprêtre, MD, Kirsten Fischer, MD, Ursula Vehling-Kaiser, MD, Barbara Eichhorst, MD, Manuela A. Bergmann, MD, Stephan Stilgenbauer, MD, Hartmut Döhner, MD, Veronique Leblond, MD, Michael Hallek, MD, and Vincent Levy, MD, PhD. Early Versus Deferred Treatment With Combined Fludarabine, Cyclophosphamide and Rituximab (FCR) Improves Event-Free Survival In Patients With High-Risk Binet Stage A Chronic Lymphocytic Leukemia – First Results Of a Randomized German-French Cooperative Phase III Trial. 2013 ASH Annual Symposium abstract 524 [http://bloodjournal.hematologylibrary.org/content/122/21/524 link to abstract]
-# Barbara Eichhorst, MD, Anna-Maria Fink, MD, Raymonde Busch, PhD, Elisabeth Lange, MD, Hubert Köppler, Prof. Dr., Michael Kiehl, MD, Martin Sökler, MD, Rudolf Schlag, MD, Ursula Vehling-Kaiser, MD, Georg Köchling, MD, Christoph Plöger, MD, Michael Gregor, MD, Torben Plesner, MD, Marek Trneny, MD, Ph.D., Prof, Kirsten Fischer, MD, Hartmut Döhner, MD, Michael Kneba, MD, Clemens Wendtner, MD, Wolfram Klapper, Karl-Anton Kreuzer, Dr. med., Stephan Stilgenbauer, MD, Sebastian Böttcher, MD, and Michael Hallek, MD. Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG). 2013 ASH Annual Symposium abstract 526 [http://bloodjournal.hematologylibrary.org/content/122/21/526 link to abstract]
-==Fludarabine (Fludara)==
-===Regimen #1, Rai et al. 2000 (CALGB 9011); Leporrier et al. 2001; Eichorst et al. 2006 (GCLLSG CLL4); Flinn et al. 2007 (ECOG E2997); Catovsky et al. 2007 (LRF CLL4); Eichhorst et al. 2009 (GCLLSG CLL5)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 5
-'''28-day cycles x up to 6 to 12 cycles'''
-===Regimen #2, Catovsky et al. 2007===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 40 mg/m2 PO once per day on days 1 to 5
-'''28-day cycles x up to 6 to 12 cycles'''
-===References===
-# Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C; French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001 Oct 15;98(8):2319-25. [http://bloodjournal.hematologylibrary.org/content/98/8/2319.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11588025 PubMed]
-# Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [http://www.nejm.org/doi/full/10.1056/NEJM200012143432402 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11114313 PubMed]
-# Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jäger U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Döhner H, Brittinger G, Emmerich B, Hallek M; German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006 Feb 1;107(3):885-91. Epub 2005 Oct 11. [http://bloodjournal.hematologylibrary.org/content/107/3/885.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16219797 PubMed]
-# Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, Hussein MA, Appelbaum FR, Larson RA, Moore DF Jr, Tallman MS. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007 Mar 1;25(7):793-8. Epub 2007 Feb 5. [http://jco.ascopubs.org/content/25/7/793.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17283364 PubMed]
-# Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2961125-8/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17658394 PubMed]
-# Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhöfer N, Rohrberg R, Söling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Döhner H, Emmerich B, Hallek M; German CLL Study Group (GCLLSG). First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15;114(16):3382-91. Epub 2009 Jul 15. [http://bloodjournal.hematologylibrary.org/content/114/16/3382.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19605849 PubMed]
-# Manuela A. Bergmann, MD, Raymonde Busch, PhD, Barbara Eichhorst, MD, Andreas Buehler, MD, Norbert Fischer, MD, Michael J Eckart, MD, Ursula Vehling-Kaiser, MD, Ulrich Jäger, MD, Georg Hopfinger, MD, Clemens Wendtner, MD, Kirsten Fischer, MD, Bertold Emmerich, MD, Hartmut Döhner, MD, Michael Hallek, M.D. Ph.D. and Stephan Stilgenbauer, MD. Overall Survival In Early Stage Chronic Lymphocytic Leukemia Patients With Treatment Indication Due To Disease Progression: Follow-Up Data Of The CLL1 Trial Of The German CLL Study Group (GCLLSG). 2013 ASH Annual Symposium [https://ash.confex.com/ash/2013/webprogram/Paper63685.html link to abstract]
-==Fludarabine & Prednisone==
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 30 mg/m2 IV over 30 minutes once per day on days 1 to 5
-*[[Prednisone (Sterapred)]] 30 mg/m2 PO once per day on days 1 to 5
-'''28-day cycles'''
-===References===
-# O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood. 1993 Sep 15;82(6):1695-700. [http://bloodjournal.hematologylibrary.org/content/82/6/1695.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8400226 PubMed]
-# Keating MJ, O'Brien S, Lerner S, Koller C, Beran M, Robertson LE, Freireich EJ, Estey E, Kantarjian H. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood. 1998 Aug 15;92(4):1165-71. [http://bloodjournal.hematologylibrary.org/content/92/4/1165.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/9694704 PubMed]
-==FR==
-FR: '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab
-===Regimen, Byrd et al. 2003 (CALGB 9712)===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV over 20 to 30 minutes once per day on days 1 to 5
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1 & 4 of cycle 1; then [[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 of cycles 2 to 6
-Supportive medications:
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 14 of cycle 1
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-'''28-day cycles x 6 cycles'''
-If restaging done 2 months after 6 cycles of therapy shows stable disease or better, patient were then treated with:
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-'''28-day course'''
-===References===
-# Byrd JC, Peterson BL, Morrison VA, Park K, Jacobson R, Hoke E, Vardiman JW, Rai K, Schiffer CA, Larson RA. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003 Jan 1;101(1):6-14. Epub 2002 Jul 5. [http://bloodjournal.hematologylibrary.org/content/101/1/6.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12393429 PubMed]
-# '''Update:''' Byrd JC, Rai K, Peterson BL, Appelbaum FR, Morrison VA, Kolitz JE, Shepherd L, Hines JD, Schiffer CA, Larson RA. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005 Jan 1;105(1):49-53. Epub 2004 May 11. [http://bloodjournal.hematologylibrary.org/content/105/1/49.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15138165 PubMed]
-==HDMP-R==
-HDMP-R: '''<u>H</u>'''igh '''<u>D</u>'''ose, '''<u>M</u>'''ethyl'''<u>P</u>'''rednisolone, '''<u>R</u>'''ituximab
-===Regimen, Castro et al. 2009===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Methylprednisolone (Solumedrol)]] 1000 mg/m2 IV over 90 minutes once per day on days 1 to 3
-*[[Rituximab (Rituxan)]] 375 mg/m2 total divided over 2 days IV once on days 1 & 2 of cycle 1; then 375 mg/m2 IV once on days 8, 15, 22 of cycle 1; then [[Rituximab (Rituxan)]] 375 mg/m2 IV once on days 1, 8, 15, 22 of cycles 2 to 3
-Supportive medications:
-*[[Cimetidine]] as premedication for [[Methylprednisolone (Solumedrol)]]
-*[[Acetaminophen (Tylenol)]] as premedication for [[Rituximab (Rituxan)]]
-*[[Diphenhydramine (Benadryl)]] as premedication for [[Rituximab (Rituxan)]]
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] (or equivalent) prophylaxis during therapy and continuing for 2 months after treatment is complete
-*[[Acyclovir (Zovirax)]] (or equivalent) prophylaxis during therapy and continuing for 2 months after treatment is complete
-*[[Fluconazole (Diflucan)]] (or equivalent) prophylaxis during therapy and continuing for 2 months after treatment is complete
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day, started 3 days before the start of therapy and continued during treatment
-*Patients with glucose >200 on days of treatment received regular insulin SC sliding scale on days of treatment
-'''28-day cycles x 3 cycles'''
-===References===
-# Castro JE, James DF, Sandoval-Sus JD, Jain S, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia. 2009 Oct;23(10):1779-89. Epub 2009 Aug 20. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761991/?tool=pubmed link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19693094 PubMed]
-==Ibrutinib (Imbruvica)==
-===Regimen, O'Brien et al. 2013===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-''Although both 420 mg and 840 mg doses were planned, the 840 mg cohort was closed due to findings of comparable efficacy in other studies.''
-*[[Ibrutinib (Imbruvica)]] 420 mg once per day
-'''28-day cycles, given until progression of disease or unacceptable toxicity'''
-===References===
-# O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA, Grant B, Richards DA, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Izumi R, Hamdy A, Chang BY, Graef T, Clow F, Buggy JJ, James DF, Byrd JC. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014 Jan;15(1):48-58. Epub 2013 Dec 10. [http://www.sciencedirect.com/science/article/pii/S1470204513705138 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24332241 PubMed]
-==Idelalisib & Rituximab==
-===Regimen, O'Brien et al. 2013===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Idelalisib (CAL-101)]] 150 mg PO BID x 48 weeks
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week x 8 weeks
-'''48-week treatment; patients who had not progressed could continue on an extension study'''
-===References===
-# Susan Mary O'Brien, Nicole Lamanna, Thomas J. Kipps, Ian Flinn, Andrew David Zelenetz, Jan Andreas Burger, Leanne Holes, David Michael Johnson, Jessie Gu, Roger D. Dansey, Ronald L. Dubowy, Steven E. Coutre. A phase II study of the selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor idelalisib (GS-1101) in combination with rituximab (R) in treatment-naive patients (pts) ≥65 years with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). J Clin Oncol 31, 2013 (suppl; abstr 7005) [http://meetinglibrary.asco.org/content/117245-132 link to abstract]
-==Lenalidomide (Revlimid)==
-===Regimen #1, Badoux et al. 2011; Strati et al. 2013===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Lenalidomide (Revlimid)]] 5 mg PO once per day on days 1 to 56, then increased to a target dose of 25 mg PO once per day
-'''Continue until progression'''
-===Regimen #2, Chen et al. 2010 & 2014===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Lenalidomide (Revlimid)]] 2.5 mg PO once per day on days 1 to 21 of cycle 1; increased if tolerated to 5 mg PO once per day on days 1 to 21 of cycle 2; increased if tolerated to 10 mg PO once per day on days 1 to 21 of subsequent cycles
-Supportive medications:
-*[[Aspirin]] 81 mg PO once per day
-'''28-day cycles'''
-===References===
-# Chen CI, Bergsagel PL, Paul H, Xu W, Lau A, Dave N, Kukreti V, Wei E, Leung-Hagesteijn C, Li ZH, Brandwein J, Pantoja M, Johnston J, Gibson S, Hernandez T, Spaner D, Trudel S. Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia. J Clin Oncol. 2011 Mar 20;29(9):1175-81. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/9/1175.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21189385 PubMed]
-# Badoux XC, Keating MJ, Wen S, Lee BN, Sivina M, Reuben J, Wierda WG, O'Brien SM, Faderl S, Kornblau SM, Burger JA, Ferrajoli A. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood. 2011 Sep 29;118(13):3489-98. Epub 2011 Jul 1. [http://bloodjournal.hematologylibrary.org/content/118/13/3489.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21725050 PubMed]
-# '''Update:''' Strati P, Keating MJ, Wierda WG, Badoux XC, Calin S, Reuben JM, O'Brien S, Kornblau SM, Kantarjian HM, Gao H, Ferrajoli A. Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia. Blood. 2013 Jun 25. [Epub ahead of print] [http://bloodjournal.hematologylibrary.org/content/early/2013/06/25/blood-2013-04-495341.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23801633 PubMed]
-# '''Update:''' Christine I. Chen, Harminder Paul, Trina Wang, Lisa W. Le, Nimisha Dave, Vishal Kukreti, Ellen Nong Wei, Anthea Lau, Peter Leif Bergsage, Suzanne Trudel. Long-term follow-up of a phase 2 trial of single agent lenalidomide in previously untreated patients with chronic lymphocytic leukaemia. [Epub ahead of print] [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12785/full link to original article]
-==Lenalidomide & Rituximab==
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-''This combination was only studied in SLL (as opposed to CLL).''
-*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21, with "monthly dose escalation" (details not described)
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
-'''28-day cycles up to 12 cycles'''
-===References===
-# N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==53803 link to abstract]
-# Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/901 link to abstract]
-==O-FC==
-O-FC: '''<u>O</u>'''fatumumab, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Ofatumumab (Arzerra)]] 300 mg IV once on day 1 of cycle 1; then 500 mg or 1000 mg IV once on day 1 of cycles 2 to 6
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 2 to 4 of cycle 1; then 25 mg/m2 IV once per day on days 1 to 3 of subsequent cycles (note: there was ambiguity in Wierda et al. 2011 about whether both fludarabine and cyclophosphamide are given three days per cycle, or whether fludarabine is given once per cycle and only cyclophosphamide is given three days per cycle)
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 2 to 4 of cycle 1; then 250 mg/m2 IV once per day on days 1 to 3 of subsequent cycles
-Supportive medications:
-*[[Acetaminophen (Tylenol)]] 1000 mg PO as premedication prior to [[Ofatumumab (Arzerra)]]
-*[[Cetirizine (Zyrtec)]] 10 mg (or equivalent) PO as premedication prior to [[Ofatumumab (Arzerra)]]
-*[[Prednisolone (Millipred)]] 100 mg ([[Steroid conversions|or equivalent]]) PO once before doses 1 & 2 of [[Ofatumumab (Arzerra)]], then reduced by physician discretion for later doses
-*May be used at physician discretion:
-**[[Allopurinol (Zyloprim)]] for tumor lysis syndrome prophylaxis
-**Antiviral and PCP (Pneumocystis jiroveci pneumonia) prophylaxis
-**Growth factor support
-'''28-day cycles x 6 cycles'''
-===References===
-# Wierda WG, Kipps TJ, Dürig J, Griskevicius L, Stilgenbauer S, Mayer J, Smolej L, Hess G, Griniute R, Hernandez-Ilizaliturri FJ, Padmanabhan S, Gorczyca M, Chang CN, Chan G, Gupta I, Nielsen TG, Russell CA; 407 Study Investigators. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood. 2011 Jun 16;117(24):6450-8. Epub 2011 Apr 15. [http://bloodjournal.hematologylibrary.org/content/117/24/6450.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21498674 PubMed]
-==PCR==
-PCR: '''<u>P</u>'''entostatin, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
-===Regimen, Kay et al. 2007 & Shanafelt et al. 2007===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Pentostatin (Nipent)]] 2 mg/m2 IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
-*[[Rituximab (Rituxan)]] 100 mg/m2 IV once on cycle 1 day 1, then 375 mg/m2 IV once on days 3 & 5 of cycle 1; then 375 mg/m2 IV once on day 1 of cycles 2 to 6
-Supportive medications (see references for details, as they differ by paper):
-*[[Filgrastim (Neupogen)]] once per day starting on day 3 x up to 10 days or until ANC >1 x 10^9/L for 2 straight days
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 15 of cycle 1
-*Prophylactic [[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] x 1 year
-*Prophylactic [[Acyclovir (Zovirax)]] x 1 year
-'''28-day cycles x 6 cycles'''
-===References===
-# Kay NE, Geyer SM, Call TG, Shanafelt TD, Zent CS, Jelinek DF, Tschumper R, Bone ND, Dewald GW, Lin TS, Heerema NA, Smith L, Grever MR, Byrd JC. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood. 2007 Jan 15;109(2):405-11. Epub 2006 Sep 28. [http://bloodjournal.hematologylibrary.org/content/109/2/405.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17008537 PubMed]
-# Shanafelt TD, Lin T, Geyer SM, Zent CS, Leung N, Kabat B, Bowen D, Grever MR, Byrd JC, Kay NE. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer. 2007 Jun 1;109(11):2291-8. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22662/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17514743 PubMed]
-==Placebo (Observation)==
-===Regimen, Dighiero et al. 1998; Bergmann et al. 2013 (GCLLSG CLL1); Schweighofer et al. 2013 (GCLLSG CLL7)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''No treatment. Placed here because one or more randomized clinical trials included a placebo arm in this disease context. Note that in both Dighiero et al. 1998 and Bergmann et al. 2013, the treatment arm was not superior to the placebo arm, reinforcing the "watch and wait" approach for early stage CLL. Whereas, Schweighofer et al. 2013 show that early FCR improves event-free survival.''
-===References===
-# Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet JL, Travade P. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med. 1998 May 21;338(21):1506-14. [http://www.nejm.org/doi/full/10.1056/NEJM199805213382104#t=article link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9593789 PubMed]
-# Manuela A. Bergmann, MD, Raymonde Busch, PhD, Barbara Eichhorst, MD, Andreas Buehler, MD, Norbert Fischer, MD, Michael J Eckart, MD, Ursula Vehling-Kaiser, MD, Ulrich Jäger, MD, Georg Hopfinger, MD, Clemens Wendtner, MD, Kirsten Fischer, MD, Bertold Emmerich, MD, Hartmut Döhner, MD, Michael Hallek, M.D. Ph.D. and Stephan Stilgenbauer, MD. Overall Survival In Early Stage Chronic Lymphocytic Leukemia Patients With Treatment Indication Due To Disease Progression: Follow-Up Data Of The CLL1 Trial Of The German CLL Study Group (GCLLSG). 2013 ASH Annual Symposium abstract 4127 [https://ash.confex.com/ash/2013/webprogram/Paper63685.html link to abstract]
-# Carmen D Schweighofer, MD, Florence Cymbalista, MD, Carolin Müller, MD, Raymonde Busch, PhD, Raphael Porcher, PhD, Petra Langerbeins, MD, Bruno Cazin, MD, Anna-Maria Fink, MD, Brigitte Dreyfus, MD, Stefan Ibach, Stéphane Leprêtre, MD, Kirsten Fischer, MD, Ursula Vehling-Kaiser, MD, Barbara Eichhorst, MD, Manuela A. Bergmann, MD, Stephan Stilgenbauer, MD, Hartmut Döhner, MD, Veronique Leblond, MD, Michael Hallek, MD, and Vincent Levy, MD, PhD. Early Versus Deferred Treatment With Combined Fludarabine, Cyclophosphamide and Rituximab (FCR) Improves Event-Free Survival In Patients With High-Risk Binet Stage A Chronic Lymphocytic Leukemia – First Results Of a Randomized German-French Cooperative Phase III Trial. 2013 ASH Annual Symposium abstract 524 [http://bloodjournal.hematologylibrary.org/content/122/21/524 link to abstract]
-==Rituximab (Rituxan)==
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-*Optional alternate dosing for patients with WBC count >100 x 10<sup>3</sup>/uL:
-**[[Rituximab (Rituxan)]] 100 mg IV once on day 1, with remainder of the 375 mg/m2 dosage given once on day 2
-Initial infusion rate with first dose of rituximab: 50 mg/H, then increased as tolerated by 50 mg/H every 30 minutes to a maximum of 400 mg/H
-Infusion rate with subsequent doses of rituximab (if first dose tolerated): 100 mg/H, then increased as tolerated by 100 mg/H ever 30 minutes to a maximum of 400 mg/H
-Supportive medications:
-*If WBC >50 or massive lymphadenopathy: [[Allopurinol (Zyloprim)]] 300 mg PO once per day starting 3 days before the first dose of [[Rituximab (Rituxan)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Cimetidine (Tagamet)]] 300 mg OR [[Ranitidine (Zantac)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-'''28-day cycles x 6 cycles'''
-Patients with response or stable disease then received:
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-Supportive medications:
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Cimetidine (Tagamet)]] 300 mg OR [[Ranitidine (Zantac)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-'''6-month cycles x 4 cycles'''
-===References===
-# Hainsworth JD, Litchy S, Barton JH, Houston GA, Hermann RC, Bradof JE, Greco FA; Minnie Pearl Cancer Research Network. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2003 May 1;21(9):1746-51. [http://jco.ascopubs.org/content/21/9/1746.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12721250 PubMed]
-=Maintenance=
-==Observation==
-===Regimen===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''No treatment; used as a comparator arm and here for reference purposes only.''
-===References===
-# Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
-==Rituximab (Rituxan)==
-===Regimen #1, Hainsworth et al. 2002===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-*Optional alternate dosing for patients with WBC count >100 x 10<sup>3</sup>/uL:
-**[[Rituximab (Rituxan)]] 100 mg IV once on day 1, with remainder of the 375 mg/m2 dosage given once on day 2
-Initial infusion rate with first dose of rituximab: 50 mg/H, then increased as tolerated by 50 mg/H every 30 minutes to a maximum of 400 mg/H
-Infusion rate with subsequent doses of rituximab (if first dose tolerated): 100 mg/H, then increased as tolerated by 100 mg/H ever 30 minutes to a maximum of 400 mg/H
-Supportive medications:
-*If WBC >50 or massive lymphadenopathy: [[Allopurinol (Zyloprim)]] 300 mg PO once per day starting 3 days before the first dose of [[Rituximab (Rituxan)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Cimetidine (Tagamet)]] 300 mg OR [[Ranitidine (Zantac)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-'''28-day cycles x 6 cycles'''
-Patients with response or stable disease then received:
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-Supportive medications:
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Cimetidine (Tagamet)]] 300 mg OR [[Ranitidine (Zantac)]] 50 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-'''6-month cycles x 4 cycles'''
-===Regimen #2, Hochster et al. 2009 (ECOG1496)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-'''Four courses, every 6 months (16 total doses)'''
-===References===
-# Hainsworth JD, Litchy S, Barton JH, Houston GA, Hermann RC, Bradof JE, Greco FA; Minnie Pearl Cancer Research Network. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2003 May 1;21(9):1746-51. [http://jco.ascopubs.org/content/21/9/1746.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12721250 PubMed]
-# Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
-=Relapsed/refractory=
-==Alemtuzumab (Campath)==
-===Regimen #1, Keating et al. 2002; Rai et al. 2002===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Alemtuzumab (Campath)]] 3 mg IV once per day, then increased as tolerated in terms of infusion reactions to [[Alemtuzumab (Campath)]] 10 mg IV once per day, and then to [[Alemtuzumab (Campath)]] 30 mg IV once per day.  Once 30 mg dose is tolerated, administer [[Alemtuzumab (Campath)]] 30 mg IV over 2 hours, 3 times per week
-Supportive medications (see references for details, as they differ by paper):
-*[[Diphenhydramine (Benadryl)]] 50 mg PO once 30 minutes prior to [[Alemtuzumab (Campath)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Alemtuzumab (Campath)]]
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO 3 times per week, starting on day 8, continuing at a minimum until 2 months after treatment is complete
-*[[Famciclovir (Famvir)]] 250 mg PO BID, starting on day 8, continuing at a minimum until 2 months after treatment is complete
-'''up to 12 to 16 weeks of therapy;''' total course varies depending on reference
-===Regimen #2, Lozanski et al. 2004===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Alemtuzumab (Campath)]] 3 mg IV once on day 1, then [[Alemtuzumab (Campath)]] 10 mg IV once on day 2, then [[Alemtuzumab (Campath)]] 30 mg IV once on day 3, then [[Alemtuzumab (Campath)]] 30 mg IV 3 days per week
-Supportive medications:
-*[[Filgrastim (Neupogen) | G-CSF]] or [[Sargramostim (Leukine) | GM-CSF]] per institutional protocol
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO 3 times per week during therapy and continued for 6 months after treatment is complete
-*[[Acyclovir (Zovirax)]] 800 mg PO TID during therapy and continued for 6 months after treatment is complete; similar medication can be used if intolerant of acyclovir
-'''12 weeks of therapy'''
-===References===
-# Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002 May 15;99(10):3554-61. [http://bloodjournal.hematologylibrary.org/content/99/10/3554.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11986207 PubMed]
-# Rai KR, Freter CE, Mercier RJ, Cooper MR, Mitchell BS, Stadtmauer EA, Santábarbara P, Wacker B, Brettman L. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002 Sep 15;20(18):3891-7. [http://jco.ascopubs.org/content/20/18/3891.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12228210 PubMed]
-# Lozanski G, Heerema NA, Flinn IW, Smith L, Harbison J, Webb J, Moran M, Lucas M, Lin T, Hackbarth ML, Proffitt JH, Lucas D, Grever MR, Byrd JC. Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004 May 1;103(9):3278-81. Epub 2004 Jan 15. [http://bloodjournal.hematologylibrary.org/content/103/9/3278.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14726385 PubMed]
-==Alemtuzumab & Rituximab==
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Alemtuzumab (Campath)]] 3 mg IV once on day 1, 10 mg IV once on day 2, 30 mg IV once on day 3 of week 1, then 30 mg IV once per day on days 10, 12, 17, 19, 24, 26 (i.e. days 3 and 5 of weeks 2 to 4)
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
-**For patients with WBC >50,000/uL, the first dose of [[Rituximab (Rituxan)]] was split into 100 mg/m2 IV once on day 1 and 275 mg/m2 IV once on day 2
-Supportive medications:
-*Prophylactic [[Trimethoprim/Sulfamethoxazole (Bactrim DS)]], given during therapy and continuing at a minimum until 2 months after treatment is complete
-*Prophylactic [[Valacyclovir (Valtrex)]] (or equivalent), given during therapy and continuing at a minimum until 2 months after treatment is complete
-'''28-day cycles x 1 to 2 cycles depending on response and toxicity'''
-===References===
-# Faderl S, Thomas DA, O'Brien S, Garcia-Manero G, Kantarjian HM, Giles FJ, Koller C, Ferrajoli A, Verstovsek S, Pro B, Andreeff M, Beran M, Cortes J, Wierda W, Tran N, Keating MJ. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood. 2003 May 1;101(9):3413-5. Epub 2003 Jan 9. [http://bloodjournal.hematologylibrary.org/content/101/9/3413.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12522009 Pubmed]
-==Bendamustine (Treanda)==
-===Regimen #1, Niederle et al. 2013===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Bendamustine (Treanda)]] 100 mg/m2 IV over 30 minutes once on days 1 & 2
-'''28-day cycles x 6 cycles;''' Niederle et al. 2013 treated patients for up to 8 cycles
-===Regimen #2, Friedberg et al. 2008; Kahl et al. 2010===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Bendamustine (Treanda)]] 120 mg/m2 IV over 60 to 120 minutes once on days 1 & 2
-'''21-day cycle x 6 to 8 cycles (up to 12 in Friedberg et al. 2008)'''
-===References===
-<!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, Florida -->
-# Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. [http://jco.ascopubs.org/content/26/2/204.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18182663 PubMed]
-<!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
-# Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a Multicenter Study. Cancer. 2010 Jan 1;116(1):106-14. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24714/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19890959 PubMed]
-# Niederle N, Megdenberg D, Balleisen L, Heit W, Knauf W, Weiß J, Freier W, Hinke A, Ibach S, Eimermacher H. Bendamustine compared to fludarabine as second-line treatment in chronic lymphocytic leukemia. Ann Hematol. 2013 May;92(5):653-60. Epub 2013 Jan 23. [http://link.springer.com/article/10.1007%2Fs00277-012-1660-6 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23340738 PubMed]
-# '''Retrospective:''' Kolibaba KS, Sterchele JA, Joshi AD, Forsyth M, Alwon E, Beygi H, Kennealey GT. Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study. Ther Adv Hematol. 2013 Jun;4(3):157-71. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666446/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23730494 PubMed]
-==BendOfa==
-BendOfa: '''<u>Bend</u>'''amustine, '''<u>Ofa</u>'''tumumab
-===Regimen, Cortelezzi et al. 2013 (GIMEMA CLL0809)===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Bendamustine (Treanda)]] 70 mg/m2 IV once per day on days 1 & 2
-*[[Ofatumumab (Arzerra)]] as follows:
-**[[Ofatumumab (Arzerra)]] 300 mg IV once on day 1 of cycle 1, then 1000 mg IV once on day 7 of cycle 1
-**[[Ofatumumab (Arzerra)]] 1000 mg IV once on day 1 of subsequent cycles
-Supportive medications:
-*[[Acetaminophen (Tylenol)]] 1000 mg PO prior to [[Ofatumumab (Arzerra)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg PO prior to [[Ofatumumab (Arzerra)]]
-*[[Methylprednisolone (Solumedrol)]] 40 mg IV prior to [[Ofatumumab (Arzerra)]]
-*[[Allopurinol (Zyloprim)]] or [[Rasburicase (Elitek)]] required for prophylaxis against TLS; dose not specified
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] required; dose not specified
-*[[Acyclovir (Zovirax)]] required; dose not specified
-'''28-day cycle up to 6 cycles'''
-===References===
-# Cortelezzi A, Sciumè M, Liberati AM, Vincenti D, Cuneo A, Reda G, Laurenti L, Zaja F, Marasca R, Chiarenza A, Gritti G, Orsucci L, Storti S, Angelucci E, Cascavilla N, Gobbi M, Mauro FR, Morabito F, Fabris S, Piciocchi A, Vignetti M, Neri A, Rossi D, Giannarelli D, Guarini A, Foà R. Bendamustine in combination with Ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. Leukemia. 2014 Mar;28(3):642-8. Epub 2013 Nov 13. [http://www.nature.com/leu/journal/v28/n3/full/leu2013334a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24220274 PubMed]
-==BR==
-BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Bendamustine (Treanda)]] 70 mg/m2 IV once per day on days 1 & 2
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 0 of the first cycle, then 500 mg/m2 IV once on day 1 on cycle 2 and subsequent cycles
-'''28-day cycles x up to 6 cycles based on response and toxicity'''
-===References===
-# Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, Schweighofer CD, Böttcher S, Staib P, Kiehl M, Eckart MJ, Kranz G, Goede V, Elter T, Bühler A, Winkler D, Kneba M, Döhner H, Eichhorst BF, Hallek M, Wendtner CM. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011 Sep 10;29(26):3559-66. Epub 2011 Aug 15. [http://jco.ascopubs.org/content/29/26/3559.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21844497 PubMed]
-# '''Retrospective:''' Kolibaba KS, Sterchele JA, Joshi AD, Forsyth M, Alwon E, Beygi H, Kennealey GT. Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study. Ther Adv Hematol. 2013 Jun;4(3):157-71. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666446/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23730494 PubMed]
-==CFAR==
-CFAR: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''ludarabine, '''<u>A</u>'''lemtuzumab, '''<u>R</u>'''ituximab
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 3 to 5
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 3 to 5
-*[[Alemtuzumab (Campath)]] 30 mg IV once per day on days 1, 3, 5
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 2 of cycle 1; then 500 mg/m2 IV once on day 2 of cycles 2 to 6
-Supportive medications:
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 7 of cycle 1
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO BID
-*Antiviral prophylaxis with:
-**EITHER [[Valacyclovir (Valtrex)]] 500 mg PO once per day
-**OR [[Valgancyclovir (Valcyte)]] 450 mg PO BID
-*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
-*At physician's discretion:
-**[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]/[[Alemtuzumab (Campath)]]
-**[[Diphenhydramine (Benadryl)]] 25 to 50 mg PO/IV once 30 minutes prior to [[Rituximab (Rituxan)]]/[[Alemtuzumab (Campath)]]
-**[[Hydrocortisone (Cortef)]] 100 mg IV once 30 minutes prior to [[Alemtuzumab (Campath)]]
-'''28-day cycles x 6 cycles'''
-===References===
-# Badoux XC, Keating MJ, Wang X, O'Brien SM, Ferrajoli A, Faderl S, Burger J, Koller C, Lerner S, Kantarjian H, Wierda WG. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia. Blood. 2011 Aug 25;118(8):2085-93. Epub 2011 Jun 13. [http://bloodjournal.hematologylibrary.org/content/118/8/2085.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21670470 PubMed]
-==Cladribine (Leustatin)==
-===Regimen, Robak et al. 2006 (PALG CLL2)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 2 hours once per day on days 1 to 5
-'''28-day cycles x up to 6 cycles'''
-===References===
-# Robak T, Blonski JZ, Gora-Tybor J, Jamroziak K, Dwilewicz-Trojaczek J, Tomaszewska A, Konopka L, Ceglarek B, Dmoszynska A, Kowal M, Kloczko J, Stella-Holowiecka B, Sulek K, Calbecka M, Zawilska K, Kuliczkowski K, Skotnicki AB, Warzocha K, Kasznicki M; Polish Leukemia Group (PALG CLL2). Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood. 2006 Jul 15;108(2):473-9. Epub 2006 Mar 21. [http://bloodjournal.hematologylibrary.org/content/108/2/473.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16551966 PubMed]
-==CC==
-CC: '''<u>C</u>'''ladribine, '''<u>C</u>'''yclophosphamide
-===Regimen, Robak et al. 2006 (PALG CLL2)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 2 hours once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 650 mg/m2 IV once on day 1
-Supportive medications:
-*"No routine prophylaxis with antibiotics, antiviral agents, or growth factors."
-'''28-day cycles x up to 6 cycles'''
-===References===
-# Robak T, Blonski JZ, Gora-Tybor J, Jamroziak K, Dwilewicz-Trojaczek J, Tomaszewska A, Konopka L, Ceglarek B, Dmoszynska A, Kowal M, Kloczko J, Stella-Holowiecka B, Sulek K, Calbecka M, Zawilska K, Kuliczkowski K, Skotnicki AB, Warzocha K, Kasznicki M; Polish Leukemia Group (PALG CLL2). Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood. 2006 Jul 15;108(2):473-9. Epub 2006 Mar 21. [http://bloodjournal.hematologylibrary.org/content/108/2/473.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16551966 PubMed]
-==CMC==
-CMC: '''<u>C</u>'''ladribine, '''<u>M</u>'''itoxantrone, '''<u>C</u>'''yclophosphamide
-===Regimen, Robak et al. 2006 (PALG CLL2)===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 2 hours once per day on days 1 to 3
-*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]] 650 mg/m2 IV once on day 1
-'''28-day cycles x up to 6 cycles'''
-===References===
-# Robak T, Blonski JZ, Gora-Tybor J, Jamroziak K, Dwilewicz-Trojaczek J, Tomaszewska A, Konopka L, Ceglarek B, Dmoszynska A, Kowal M, Kloczko J, Stella-Holowiecka B, Sulek K, Calbecka M, Zawilska K, Kuliczkowski K, Skotnicki AB, Warzocha K, Kasznicki M; Polish Leukemia Group (PALG CLL2). Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood. 2006 Jul 15;108(2):473-9. Epub 2006 Mar 21. [http://bloodjournal.hematologylibrary.org/content/108/2/473.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16551966 PubMed]
-==FC==
-FC: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide
-===Regimen, Robak et al. 2010===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 1 to 3
-'''28-day cycles x 6 cycles'''
-Supportive medications (varied according to reference):
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 7 of cycle 1
-*Some patients received:
-**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO two times per week
-**[[Valacyclovir (Valtrex)]] 500 mg once per day
-===References===
-# Robak T, Dmoszynska A, Solal-Céligny P, Warzocha K, Loscertales J, Catalano J, Afanasiev BV, Larratt L, Geisler CH, Montillo M, Zyuzgin I, Ganly PS, Dartigeas C, Rosta A, Maurer J, Mendila M, Saville MW, Valente N, Wenger MK, Moiseev SI. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1756-65. Epub 2010 Mar 1. [http://jco.ascopubs.org/content/28/10/1756.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20194844 PubMed] content property of [http://hemonc.org HemOnc.org]
-==FCR==
-FCR: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
-===Regimen #1, Tam et al. 2006===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV over 15 to 30 minutes once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV over 15 to 30 minutes once per day on days 1 to 3
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
-'''28-day cycles x up to 6 cycles or "attainment of maximum response"'''
-===Regimen #2, Robak et al. 2010===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 250 mg/m2 IV once per day on days 1 to 3
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 of cycle 1; then 500 mg/m2 IV once on day 1 of cycles 2 to 6
-Supportive medications (varied according to reference):
-*[[Diphenhydramine (Benadryl)]] 25 mg IV once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once 30 minutes prior to [[Rituximab (Rituxan)]]
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 7 of cycle 1
-*Some patients received:
-**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO two times per week
-**[[Valacyclovir (Valtrex)]] 500 mg once per day
-'''28-day cycles x 6 cycles'''
-===References===
-# Tam CS, Wolf M, Prince HM, Januszewicz EH, Westerman D, Lin KI, Carney D, Seymour JF. Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma. Cancer. 2006 Jun 1;106(11):2412-20. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21882/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16649223 PubMed]
-# Robak T, Dmoszynska A, Solal-Céligny P, Warzocha K, Loscertales J, Catalano J, Afanasiev BV, Larratt L, Geisler CH, Montillo M, Zyuzgin I, Ganly PS, Dartigeas C, Rosta A, Maurer J, Mendila M, Saville MW, Valente N, Wenger MK, Moiseev SI. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1756-65. Epub 2010 Mar 1. [http://jco.ascopubs.org/content/28/10/1756.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20194844 PubMed] content property of [http://hemonc.org HemOnc.org]
-==FluCam==
-FluCam: '''<u>Flu</u>'''darabine, '''<u>Cam</u>'''path
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 30 mg/m2 IV once per day on days 1 to 3
-*[[Alemtuzumab (Campath)]] 3 mg IV once on day 1, 10 mg IV once on day 2, 30 mg IV once on day 3 of cycle 1; then 30 mg IV once per day on days 1 to 3 for cycles 2 to 6
-Supportive medications:
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS) | Trimethoprim/Sulfamethoxazole]] 960 mg (paper did not specify which component was 960 mg) PO once per day, started on day 1 and continued at least 2 months after treatment is complete
-*[[Valacyclovir (Valtrex)]] 500 mg PO BID, started on day 1 and continued at least 2 months after treatment is complete
-**If patients experienced CMV (cytomegalovirus) reactivation, valacyclovir was replaced by "oral or intravenous ganciclovir" 500 mg TID
-*[Fluconazole (Diflucan)]] 100 mg PO once per day, started if patients had evidence of fungal infection, continued until resolution
-*[[Acetaminophen (Tylenol)]] 1000 mg PO once prior to first dose of [[Alemtuzumab (Campath)]], then with subsequent doses if clinically indicated
-*[[Clemastine (Tavist)]] 2 mg IV once prior to first dose of [[Alemtuzumab (Campath)]], then with subsequent doses if clinically indicated
-*[[Prednisone (Sterapred)]] 100 mg IV once prior to first dose of [[Alemtuzumab (Campath)]], then with subsequent doses if clinically indicated
-*For patients with WBC >50,000/uL, bulky disease, or history of hyperuricemia: [[Allopurinol (Zyloprim)]] 300 mg PO once prior to first dose of [[Alemtuzumab (Campath)]], and used later if clinically indicated
-'''28-day cycles x 6 cycles'''
-===References===
-# Elter T, Borchmann P, Schulz H, Reiser M, Trelle S, Schnell R, Jensen M, Staib P, Schinköthe T, Stützer H, Rech J, Gramatzki M, Aulitzky W, Hasan I, Josting A, Hallek M, Engert A. Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial. J Clin Oncol. 2005 Oct 1;23(28):7024-31. Epub 2005 Sep 6. [http://jco.ascopubs.org/content/23/28/7024.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16145065 PubMed]
-==Fludarabine (Fludara)==
-===Regimen #1, Niederle et al. 2013===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV once per day on days 1 to 5
-'''28-day cycles x up to 6 to 12 cycles'''
-===References===
-# Niederle N, Megdenberg D, Balleisen L, Heit W, Knauf W, Weiß J, Freier W, Hinke A, Ibach S, Eimermacher H. Bendamustine compared to fludarabine as second-line treatment in chronic lymphocytic leukemia. Ann Hematol. 2013 May;92(5):653-60. Epub 2013 Jan 23. [http://link.springer.com/article/10.1007%2Fs00277-012-1660-6 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23340738 PubMed]
-==Fludarabine & Prednisone==
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Fludarabine (Fludara)]] 30 mg/m2 IV over 30 minutes once per day on days 1 to 5
-*[[Prednisone (Sterapred)]] 30 mg/m2 PO once per day on days 1 to 5
-'''28-day cycles'''
-===References===
-# O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood. 1993 Sep 15;82(6):1695-700. [http://bloodjournal.hematologylibrary.org/content/82/6/1695.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8400226 PubMed]
-# '''Update:''' Keating MJ, O'Brien S, Lerner S, Koller C, Beran M, Robertson LE, Freireich EJ, Estey E, Kantarjian H. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood. 1998 Aug 15;92(4):1165-71. [http://bloodjournal.hematologylibrary.org/content/92/4/1165.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/9694704 PubMed]
-==HDMP-R==
-HDMP-R: '''<u>H</u>'''igh '''<u>D</u>'''ose, '''<u>M</u>'''ethyl'''<u>P</u>'''rednisolone, '''<u>R</u>'''ituximab
-===Regimen #1, Pileckyte et al. 2011===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Methylprednisolone (Solumedrol)]] 1000 mg/m2 IV once per day over 4 hours on days 1 to 5
-*[[Rituximab (Rituxan)]] 50 mg IV once on cycle 1 day 1; 150 mg IV once on cycle 1 day 2; remainder of a 375 mg/m2 dose on cycle 1 day 3; subsequently 500 mg/m2 IV once on cycle 1 day 5 and days 1 and 5 of other cycles
-Supportive medications:
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|trimethoprim/sulfamethoxazole]] "or an equivalent antibiotic throughout the treatment period and up to 6 months after the completion of therapy"
-'''21-day cycles x 6 cycles'''
-===Regimen #2, Bowen et al. 2007===
-<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Retrospective</span>
-*[[Methylprednisolone (Solumedrol)]] 1000 mg/m2 IV once per day on days 1 to 5
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on days 1, 8, 15, 22
-Supportive medications:
-*No standard prophylaxis, but some sites used [[Trimethoprim/Sulfamethoxazole (Bactrim DS)|trimethoprim/sulfamethoxazole]] and/or [[Acyclovir (Zovirax)]]
-'''28-day cycles'''
-===References===
-# Bowen DA, Call TG, Jenkins GD, Zent CS, Schwager SM, Van Dyke DL, Jelinek DF, Kay NE, Shanafelt TD. Methylprednisolone-rituximab is an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia including those with unfavorable cytogenetic features. Leuk Lymphoma. 2007 Dec;48(12):2412-7. [http://informahealthcare.com/doi/abs/10.1080/10428190701724801 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18067017 PubMed]
-# Pileckyte R, Jurgutis M, Valceckiene V, Stoskus M, Gineikiene E, Sejoniene J, Degulys A, Zvirblis T, Griskevicius L. Dose-dense high-dose methylprednisolone and rituximab in the treatment of relapsed or refractory high-risk chronic lymphocytic leukemia. Leuk Lymphoma. 2011 Jun;52(6):1055-65. [http://informahealthcare.com/doi/full/10.3109/10428194.2011.562572 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21599591 PubMed]
-==Ibrutinib (Imbruvica)==
-===Regimen, Byrd et al. 2013===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-''Both 420 mg and 840 mg doses were investigated.  Per Byrd et al. 2013: "the similar response in the two dose groups provide support for the use of the 420-mg dose of ibrutinib for relapsed CLL."''
-*[[Ibrutinib (Imbruvica)]] 420 mg PO once per day
-'''given until progression of disease or unacceptable toxicity'''
-===References===
-# Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, O'Brien S. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Jul 4;369(1):32-42. [http://www.nejm.org/doi/full/10.1056/NEJMoa1215637 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23782158 PubMed]
-==Lenalidomide (Revlimid)==
-===Regimen #1, Chanan-Khan et al. 2006===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Lenalidomide (Revlimid)]] 5 mg PO once per day, escalated by 5 mg every 1 to 2 weeks to a target maximum dose of 25 mg PO once per day on days 1 to 21
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day starting 2 to 3 days prior to therapy, and continued up to a total of 14 days
-'''28-day cycles'''
-===Regimen #2, Ferrajoli et al. 2008===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 28, then increased by 5 mg every 28 days to a target maximum dose of 25 mg PO once per day on days 1 to 28
-'''28-day cycles'''
-===Regimen #3, Witzig et al. 2009 (NHL-001)===
-<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
-*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
-'''28-day cycles until disease progression or unacceptable toxicity'''
-===References===
-# Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, Porter CW, Goodrich DW, Bernstein ZP, Wallace P, Spaner D, Mohr A, Byrne C, Hernandez-Ilizaliturri F, Chrystal C, Starostik P, Czuczman MS. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol. 2006 Dec 1;24(34):5343-9. Epub 2006 Nov 6. [http://jco.ascopubs.org/content/24/34/5343.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17088571 PubMed]
-# Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, Cohen EN, Li C, Reuben JM, Keating MJ. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008 Jun 1;111(11):5291-7. Epub 2008 Mar 11. [http://bloodjournal.hematologylibrary.org/content/111/11/5291.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18334676 PubMed]
-# Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5404-9. Epub 2009 Oct 5. [http://jco.ascopubs.org/content/27/32/5404.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19805688 PubMed]
-==Lenalidomide & Rituximab==
-===Regimen #1, Chanan-Khan et al. 2006===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Lenalidomide (Revlimid)]] 5 mg PO once per day, escalated by 5 mg every 1 to 2 weeks to a target maximum dose of 25 mg PO once per day on days 1 to 21
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15 of cycle 1; then 375 mg/m2 IV once per day on days 1 & 15 of subsequent cycles
-Supportive medications:
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day starting 2 to 3 days prior to therapy, and continued up to a total of 14 days
-'''28-day cycles'''
-===Regimen #2, Badoux et al. 2013===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 9 to 28 of cycle 1; then 10 mg PO once per day on days 1 to 28 of subsequent cycles
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22 of cycle 1; then 375 mg/m2 IV once on day 1 of cycles 3 to 12 (no rituximab dose during cycle 2)
-Supportive medications:
-*[[Allopurinol (Zyloprim)]] (dose/schedule not specified) on days 1 to 14 of cycle 1
-*No mandatory antibacterial, antiviral, DVT, or tumor flare prophylaxis
-*Growth factor use allowed per ASCO guidelines
-'''28-day cycles x 12 cycles (lenalidomide could continue indefinitely in responders)'''
-===References===
-# Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, Porter CW, Goodrich DW, Bernstein ZP, Wallace P, Spaner D, Mohr A, Byrne C, Hernandez-Ilizaliturri F, Chrystal C, Starostik P, Czuczman MS. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol. 2006 Dec 1;24(34):5343-9. Epub 2006 Nov 6. [http://jco.ascopubs.org/content/24/34/5343.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17088571 PubMed]
-# Badoux XC, Keating MJ, Wen S, Wierda WG, O'Brien SM, Faderl S, Sargent R, Burger JA, Ferrajoli A. Phase II Study of Lenalidomide and Rituximab As Salvage Therapy for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2013 Feb 10;31(5):584-91. Epub 2012 Dec 26. [http://jco.ascopubs.org/content/31/5/584.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23270003 PubMed]
-==OFAR==
-OFAR: '''<u>O</u>'''xaliplatin, '''<u>F</u>'''ludarabine, '''<u>A</u>'''ra-C, '''<u>R</u>'''ituximab
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Oxaliplatin (Eloxatin)]] 25 mg/m2 IV over 2 hours once per day on days 1 to 4
-*[[Fludarabine (Fludara)]] 30 mg/m2 IV once per day on days 2 & 3, adminstered within 30 minutes of completion of oxaliplantin
-*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV over 2 hours once per day on days 2 & 3, 4 hours after fludarabine started
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV over 4 to 6 hours once on day 3 of cycle 1; then 375 mg/m2 IV over 4 to 6 hours once on day 1 of cycles 2 to 6
-Supportive medications:
-*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
-*Herpes zoster and PCP (Pneumocystis jiroveci pneumonia) prophylaxis used
-'''28-day cycles x up to 6 cycles'''
-===References===
-# Tsimberidou AM, Wierda WG, Plunkett W, Kurzrock R, O'Brien S, Wen S, Ferrajoli A, Ravandi-Kashani F, Garcia-Manero G, Estrov Z, Kipps TJ, Brown JR, Fiorentino A, Lerner S, Kantarjian HM, Keating MJ. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2008 Jan 10;26(2):196-203. [http://jco.ascopubs.org/content/26/2/196.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18182662 PubMed]
-==Ofatumumab (Arzerra)==
-===Regimen===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Ofatumumab (Arzerra)]] 300 mg IV once on day 1 of cycle 1, then 2000 mg IV once per day on days 8, 15, 22 of cycle 1; then 2000 mg IV once per day on days 1, 8, 15, 22 of cycle 2; then 2000 mg IV once on day 1 of cycles 3 to 6
-Supportive medications:
-*[[Prednisolone (Millipred)]] 100 mg or [[Steroid conversions|equivalent]] once before infusions 1, 2, and 9 (question whether this was a typo), reduced to lower doses if initial infusions well-tolerated
-'''28-day cycles x 6 cycles'''
-===References===
-# Coiffier B, Lepretre S, Pedersen LM, Gadeberg O, Fredriksen H, van Oers MH, Wooldridge J, Kloczko J, Holowiecki J, Hellmann A, Walewski J, Flensburg M, Petersen J, Robak T. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008 Feb 1;111(3):1094-100. Epub 2007 Nov 14. [http://bloodjournal.hematologylibrary.org/content/111/3/1094.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18003886 PubMed]
-# Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1749-55. Epub 2010 Mar 1. [http://jco.ascopubs.org/content/28/10/1749.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20194866 PubMed]
-==PCR==
-PCR: '''<u>P</u>'''entostatin, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
-===Regimen, Lamanna et al. 2006===
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Pentostatin (Nipent)]] 4 mg/m2 IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 of cycle 2 and on (omitted from cycle 1)
-Supportive medications; paper says they were "administered prophylactically," without additional details:
-*[[Filgrastim (Neupogen)]]
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]]
-*[[Acyclovir (Zovirax)]]
-'''21-day cycles x 6 cycles'''
-===References===
-# Lamanna N, Kalaycio M, Maslak P, Jurcic JG, Heaney M, Brentjens R, Zelenetz AD, Horgan D, Gencarelli A, Panageas KS, Scheinberg DA, Weiss MA. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol. 2006 Apr 1;24(10):1575-81. Epub 2006 Mar 6. [http://jco.ascopubs.org/content/24/10/1575.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16520464 PubMed]
-==R-BAC==
-R-BAC: '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine, '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
-===Regimen===
-<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Pilot, <20 patients reported</span>
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 of the first cycle, then 500 mg/m2 IV once on day 1 of cycle 2 and subsequent cycles
-*[[Bendamustine (Treanda)]] 70 mg/m2 IV once per day over 60 minutes on days 1 & 2
-*[[Cytarabine (Cytosar)]] 800 mg/m2 IV once per day over 2 hours beginning 2 hours after bendamustine on days 1 to 3
-Supportive medications: "Primary prophylaxis with granulocyte colony-stimulating factor was routinely used starting from Day 5 after chemotherapy completion, and lasting for 3–6 days or until neutrophil count recovery."
-'''28-day cycles x up to 4 cycles with dose delay and modification based on response and toxicity'''
-===References===
-# Visco C, Finotto S, Pomponi F, Sartori R, Laveder F, Trentin L, Paolini R, Di Bona E, Ruggeri M, Rodeghiero F. The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia. Am J Hematol. 2013 Apr;88(4):289-93. Epub 2013 Feb 28. [http://onlinelibrary.wiley.com/doi/10.1002/ajh.23391/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23450436 PubMed]
-==Rituximab (Rituxan)==
-===Regimen, Furman et al. 2014===
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''This is the rituximab + placebo arm of the idelalisib phase III trial.''
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on first dose, then 500 mg/m2 IV once on subsequent doses
-'''Given every two weeks x 5 doses then every three weeks x 3 doses for 8 doses, total'''
-===References===
-# Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O'Brien SM. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2014 Jan 22. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1315226 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450857 PubMed]
-=Hairy cell leukemia=
-Regimens have been moved to [[Hairy cell leukemia]] page.

Difference between revisions of "Chronic lymphocytic leukemia"

Revision as of 17:48, 23 May 2014

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