HIV-associated lymphoma

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19 regimens on this page 25 variants on this page

Untreated

CHOP

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP

Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)

Regimen

Study	Evidence	Comparator
Kaplan et al. 2005 (AMC010)	Phase III	R-CHOP

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 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 PO once per day on days 1 to 5

Supportive medications

• Combination antiretrovirals were required
• G-CSF 5 mcg/kg SC once per day from days 4 to 13 or until ANC > 10k/ul.
• Pneumocystis cariini prophylaxis with either:
  • Cotrimoxazole (dose/route/schedule not specified)
  • Dapsone (Aczone) (dose/route/schedule not specified)
  • Pentamidine (Nebupent) (dose/schedule not specified)

21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease

Radiation therapy

Patients with stage I, IE, or nonbulky stage II disease received "involved field radiotherapy to a total dose of at least 4000 cGy beginning 3 weeks after the third cycle of chemotherapy."

References

1. Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article contains verified protocol PubMed

CODOX-M/IVAC

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CODOX-M: Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate
IVAC: Ifosfamide, Vepesid (etoposide), Ara-C (cytarabine)

Regimen

Study	Evidence
Magrath et al. 1996 (77-04)	Phase II
Wang et al. 2003	Retrospective

Note: the original protocol of Magrath et al. 1996 did not comment on HIV status. Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC.

• Patients are stratified into high and low risk:
  • Low risk patients must fulfill all of the following criteria:
    • Serum LDH within the institution's normal range (for the NCI, this was <350 IU/L)
    • Single extraabdominal mass or completely resected abdominal disease
  • Any patients which do not meet low risk criteria are classified as high risk

Part A: CODOX-M for high risk patients

• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 1, then 200 mg/m² IV once per day on days 2 to 5
• Vincristine (Oncovin) as follows:
  • Cycle 1: 1.5 mg/m² IV once per day on days 1 & 8
  • Cycle 3: 1.5 mg/m² IV once per day on days 1, 8, 15
• Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
• Methotrexate (MTX) 1200 mg/m² IV over 1 hour on day 10, then 240 mg/m²/hour IV over 23 hours on day 10 (total dose = 6720 mg/m²)

CNS prophylaxis

• Cytarabine (Cytosar) 70 mg intrathecal once per day on days 1 & 3
  • Patients younger than 3 years old received "appropriately reduced doses"
• Methotrexate (MTX) 12 mg intrathecal once on day 15
  • Patients younger than 3 years old received "appropriately reduced doses"

Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 1:

• Cytarabine (Cytosar) 70 mg intrathecal once on day 5 (in addition to doses above)
• Methotrexate (MTX) 12 mg intrathecal once on day 17 (in addition to dose above)

Supportive medications

• Folinic acid (Leucovorin) 192 mg/m² IV once on day 11, starting 36 hours after the start of the day 10 Methotrexate (MTX), then 12 mg/m² IV every 6 hours thereafter until serum methotrexate level is <5 x 10^-8 mol/L
• GM-CSF 7.5 mcg/kg SC once per day, starting on day 13 and continuing until ANC >1000/uL

Part A: CODOX-M for low risk patients

• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 1, then 200 mg/m² IV once per day on days 2 to 5
• Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1 & 8
• Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
• Methotrexate (MTX) 1200 mg/m² IV over 1 hour on day 10, then 240 mg/m²/hour IV over 23 hours on day 10 (total dose = 6720 mg/m²)

CNS prophylaxis

• Cytarabine (Cytosar) 70 mg intrathecal once on day 1
  • Patients younger than 3 years old received "appropriately reduced doses"
• Methotrexate (MTX) 12 mg intrathecal once on day 3
  • Patients younger than 3 years old received "appropriately reduced doses"

Supportive medications

• Folinic acid (Leucovorin) 192 mg/m² IV once on day 11, starting 36 hours after the start of the day 10 Methotrexate (MTX), then 12 mg/m² IV every 6 hours thereafter until serum methotrexate level is <5 x 10^-8 mol/L
• No GM-CSF used for low risk patients

Part B: IVAC for high risk patients

• Ifosfamide (Ifex) 1500 mg/m² IV once per day on days 1 to 5
• Etoposide (Vepesid) 60 mg/m² IV once per day on days 1 to 5
• Cytarabine (Cytosar) 2000 mg/m² IV every 12 hours on days 1 & 2 (total of 4 doses per cycle)

CNS prophylaxis

• Methotrexate (MTX) 12 mg intrathecal once on day 5

Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 2:

• Cytarabine (Cytosar) 70 mg intrathecal once per day on days 7 & 9
• Methotrexate (MTX) 12 mg intrathecal once on day 17 (in addition to dose above)

Supportive medications

• Mesna (Mesnex) 360 mg/m² IV every 3 hours on days 1 to 5, given at same time as Ifosfamide (Ifex)
• GM-CSF 7.5 mcg/kg SC once per day, starting on day 7 and continuing until ANC >1,000/uL

High risk patients receive Part A: CODOX-M and Part B: IVAC given in an alternating fashion x total of 4 cycles (A, B, A, B). Low risk patients receive Part A: CODOX-M x 3 cycles only. Each cycle starts on the same day that the patient's ANC is >1,000/uL.

References

1. Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. link to original article contains verified protocol PubMed
2. Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. link to original article contains verified protocol PubMed

dmCODOX-M/IVAC - Modified Magrath

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dmCODOX-M: dose-modified Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate
IVAC: Ifosfamide, Vepesid (etoposide), Ara-C (cytarabine)

Regimen

Study	Evidence
Mead et al. 2008 (MRC/NCRI LY10)	Non-randomized

• Patients are stratified into high and low risk:
  • Low risk patients must fulfill at least 3 of the following criteria:
    • Normal LDH
    • WHO performance status of 0 or 1
    • Ann Arbor stage I or II
    • 0 or 1 extranodal sites of disease
  • Any patients which do not meet low risk criteria are classified as high risk

Part A: dmCODOX-M

• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 1, then 200 mg/m² IV once per day on days 2 to 5
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg per cycle) IV once per day on days 1 & 8
• Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
• Methotrexate (MTX) as follows:
  • Patients 65 years old or younger: 300 mg/m² IV over 1 hour on day 10, then 2700 mg/m² IV over 23 hours on day 10 (total dose = 3000 mg/m²)
  • Patients older than 65 years old: 100 mg/m² IV over 1 hour on day 10, then 900 mg/m² IV over 23 hours on day 10 (total dose = 1000 mg/m²)

CNS prophylaxis

• Cytarabine (Cytosar) 70 mg intrathecal once per day on days 1 & 3
• Methotrexate (MTX) 12 mg intrathecal once on day 15

Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:

• Cytarabine (Cytosar) 70 mg intrathecal once on day 5 (in addition to doses above)
• Methotrexate (MTX) 12 mg intrathecal once on day 17 (in addition to dose above)
• Folinic acid (Leucovorin) 15 mg PO once on day 18, 24 hours after intrathecal Methotrexate (MTX)

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² IV every 3 hours x 5 doses on day 11, starting 36 hours after start of the day 10 Methotrexate (MTX), then 15 mg/m² IV every 6 hours until methotrexate level is <5 x 10^-8
• Folinic acid (Leucovorin) 15 mg PO once on day 16, 24 hours after intrathecal Methotrexate (MTX)
• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC >1000/uL
• Allopurinol (Zyloprim) PO and/or Rasburicase (Elitek) prior to starting chemotherapy

Part B: IVAC

• Ifosfamide (Ifex) as follows:
  • Patients 65 years old or younger: 1500 mg/m² IV over 1 hour once per day on days 1 to 5
  • Patients older than 65 years old: 1000 mg/m² IV over 1 hour once per day on days 1 to 5
• Etoposide (Vepesid) 60 mg/m² IV over 1 hour once per day on days 1 to 5
• Cytarabine (Cytosar) as follows:
  • Patients 65 years old or younger: 2000 mg/m² IV over 3 hours every 12 hours on days 1 & 2 (total of 4 doses per cycle)
  • Patients older than 65 years old: 1000 mg/m² IV over 3 hours every 12 hours on days 1 & 2 (total of 4 doses per cycle)

CNS prophylaxis

• Methotrexate (MTX) 12 mg intrathecal once on day 5

Supportive medications

• Mesna (Mesnex) as follows:
  • Patients 65 years old or younger: 300 mg/m² (mixed with Ifosfamide (Ifex)) IV over 1 hour on days 1 to 5, then 300 mg/m² IV every four hours x 2 doses on days 1 to 5
  • Patients older than 65 years old: 200 mg/m² (mixed with Ifosfamide (Ifex)) IV over 1 hour on days 1 to 5, then 200 mg/m² IV every four hours x 2 doses on days 1 to 5
• Folinic acid (Leucovorin) 15 mg PO once on day 6, 24 hours after intrathecal Methotrexate (MTX)
• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC >1000/uL

High risk patients receive Part A: dmCODOX-M and Part B: IVAC given in an alternating fashion x total of 4 cycles (A, B, A, B). Low risk patients receive Part A: dmCODOX-M x 3 cycles only. Each cycle starts on the same day that the patient's ANC is >1,000/uL and unsupported (that is, without transfusion) platelet count >75 x 10⁹/L

References

1. Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. link to original article contains verified protocol PubMed

DR-COP

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DR-COP: Doxil (pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin, Prednisone

Regimen

Study	Evidence
Levine et al. 2012 (AMC047)	Phase II

Chemotherapy

• Doxorubicin liposomal (Doxil) 40 mg/m² IV once on day 1
• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 750 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 PO once per day on days 1 to 5
• "CNS prophylaxis was mandated in patients with involvement of bone marrow, testis, sinuses, or epidural regions and with stage IV and/or = two extranodal sites, with specific regimen left to physician discretion."
• Highly Active Antiretroviral Therapy (HAART) required; specific regimen left to physician discretion. Use of zidovudine was not allowed.

Supportive medications

• Filgrastim (Neupogen) OR Pegfilgrastim (Neulasta) OR Sargramostim (Leukine) starting on day 3, to continue until beyond nadir of blood counts
• Erythropoietin (e.g. Epoetin alfa (Procrit) or Darbepoetin alfa (Aranesp)) at physician discretion
• PCP prophylaxis required
• Oral quinolone if CD4 cell count =100 and absolute neutrophil count (ANC) <500/uL at entry or during treatment

21 to 28 day cycle for up to 6 cycles

References

1. Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated Liposomal Doxorubicin, Rituximab, Cyclophosphamide, Vincristine, and Prednisone in AIDS-Related Lymphoma: AIDS Malignancy Consortium Study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. Epub 2012 Nov 19. link to original article link to PMC article contains verified protocol PubMed

GMALL-R

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GMALL-R: German Multicenter Study Group for the Treatment of Adult Acute Lymphoblastic Leukemia, Rituximab

Regimen

Study	Evidence
Ribera et al. 2013 (Burkimab)	Phase II

Numbering of days is based on prephase->A->B->C; however, certain patient populations received different ordering of regimen, see below.

Prephase

• Cyclophosphamide (Cytoxan) 200 mg/m² IV over 1 hour once per day on days 1 to 5
• Prednisone (Sterapred) 60 mg/m² IV bolus once per day on days 1 to 5

Cycle A

• Rituximab (Rituxan) 375 mg/m² IV over 4 hours once on day 7
• Vincristine (Oncovin) 2 mg IV bolus once on day 8
• Methotrexate (MTX) 1500 mg/m² IV over 24 hours once on day 8
  • Older than 55 years: reduce dose by 50%
• Ifosfamide (Ifex) 800 mg/m² IV over 1 hour once per day on days 8 to 12
• Dexamethasone (Decadron) 10 mg/m² IV bolus once per day on days 8 to 12
• Teniposide (Vumon) 100 mg/m² IV over 1 hour once per day on days 11 & 12
• Cytarabine (Cytosar) 150 mg/m² IV over 1 hour BID on days 11 & 12
  • Older than 55 years: reduce dose by 50%

Supportive medications

• Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion

Cycle B

• Rituximab (Rituxan) 375 mg/m² IV over 4 hours once on day 28
• Vincristine (Oncovin) 2 mg IV bolus once on day 29
• Methotrexate (MTX) 1500 mg/m² IV over 24 hours once on day 29
  • Older than 55 years: reduce dose by 50%
• Cyclophosphamide (Cytoxan) 200 mg/m² IV over 1 hour once per day on days 29 to 33
• Dexamethasone (Decadron) 10 mg/m² IV bolus once per day on days 29 to 33
• Doxorubicin (Adriamycin) 25 mg/m² IV over 15 minutes once per day on days 32 & 33

Supportive medications

• Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion

Cycle C

• Rituximab (Rituxan) 375 mg/m² IV over 4 hours once on day 49
• Vindesine (Eldisine) 3 mg/m² (maximum dose 5 mg) IV bolus once on day 50
• Methotrexate (MTX) 1500 mg/m² IV over 24 hours once on day 50
  • Older than 55 years: reduce dose by 50%
• Dexamethasone (Decadron) 10 mg/m² IV bolus once per day on days 50 to 54
• Etoposide (Vepesid) 250 mg/m² IV over 1 hour once per day on days 53 & 54
• Cytarabine (Cytosar) 2000 mg/m² IV over 3 hours BID on day 54
  • Older than 55 years: reduce dose by 50%

Supportive medications

• Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion

Give regimen as follows:

• Advanced stage and younger than 55 years: A->B->C x 2 courses (6 total cycles)
• Older than 55 years: Alternate A & B x 3 courses (6 total cycles)
• Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)

CNS Prophylaxis

• Methotrexate (MTX) 15 mg intrathecal once per day on days 1, 8, 12, 29, 33
• Cytarabine (Cytosar) 40 mg intrathecal once per day on days 1, 8, 12, 29, 33
• Dexamethasone (Decadron) 20 mg intrathecal once per day on days 1, 8, 12, 29, 33

8 doses total

References

1. Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. link to original article contains verified protocol PubMed

LMB86

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To be completed

References

1. Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, Oksenhendler E. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. Blood. 2007 Oct 15;110(8):2846-54. Epub 2007 Jul 3. link to original article PubMed

R-CHOP

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Synonyms: R-CHOP-21, CHOP-R

Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)

Regimen #1

Study	Evidence	Comparator
Kaplan et al. 2005 (AMC010)	Phase III	CHOP

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day -2
• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 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 PO once per day on days 1 to 5

Supportive medications

• Combination antiretrovirals were required
• G-CSF 5 mcg/kg SC once per day from days 4 to 13 or until ANC > 10k/ul.
• Pneumocystis cariini prophylaxis with either:
  • Cotrimoxazole (dose/schedule not specified)
  • Dapsone (Aczone) (dose/schedule not specified)
  • Pentamidine (Nebupent) (dose/schedule not specified)

21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease

Radiation therapy

Patients with stage I, IE, or nonbulky stage II disease received "involved field radiotherapy to a total dose of at least 4000 cGy beginning 3 weeks after the third cycle of chemotherapy."

Maintenance

Partial or complete responders received:

• Rituximab (Rituxan) 375 mg/m² IV once on day 1

Monthly x 3 doses

Regimen #2

Study	Evidence
Ribera et al. 2007x	Phase II

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 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) 40 mg/m² PO once per day on days 1 to 5

CNS prophylaxis

To be given with each cycle; day of administration not reported.

• Methotrexate (MTX) 12 mg intrathecal
• Cytarabine (Cytosar) 40 mg intrathecal
• Hydrocortisone (Cortef) 20 mg intrathecal

Supportive medications

• Combination antiretrovirals were required: one or two protease inhibitors and two nucleoside reverse transcriptase inhibitors
• Pneumocystis cariini prophylaxis with either:
  • Cotrimoxazole 160/800 mg PO TIW
  • Pentamidine (Nebupent) 300 mg inhaled (schedule not specified)

21-day cycle for 6 cycles

Radiation therapy

Patients with bulky disease or a residual mass received involved field radiotherapy (details not provided).

Regimen #3

Study	Evidence
Boué et al. 2006	Phase II

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day -1 (cycle 1; subsequent cycles ok to give on day 1 if tolerated)
• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 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) 40 mg/m² PO once per day on days 1 to 5

CNS prophylaxis

Decision was left to individual centers.

Supportive medications

• Antiretrovirals were recommended
• Pneumocystis cariini prophylaxis was recommended with Cotrimoxazole (dose/schedule not specified)

21-day cycle for 6 cycles

References

1. Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article contains verified protocol PubMed
2. Boué F, Gabarre J, Gisselbrecht C, Reynes J, Cheret A, Bonnet F, Billaud E, Raphael M, Lancar R, Costagliola D. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006 Sep 1;24(25):4123-8. Epub 2006 Aug 8. link to original article contains verified protocol PubMed
3. Ribera JM, Oriol A, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M; PETHEMA, GELTAMO, GELCAB and GESIDA Groups. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br J Haematol. 2008 Feb;140(4):411-9. Epub 2007 Dec 19. link to original article contains verified protocol PubMed

R-CODOX-M/R-IVAC

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R-dmCODOX-M: Rituximab, dose-modified Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate
R-IVAC: Rituximab, Ifosfamide, Vepesid (Etoposide), Ara-C (Cytarabine)

Regimen

Study	Evidence
Noy et al. 2015 (AMC 048)	Phase II

Intended for HIV-associated Burkitt lymphoma, and the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described by Lacasce et al. 2004.

Regimen A: R-CODOX-M

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 800 mg/m² IV once per day on days 1 & 2
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once per day on days 1 & 8
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Methotrexate (MTX) 3000 mg/m² IV once on day 15

CNS prophylaxis

• Cytarabine (Cytosar) 50 mg intrathecal as follows:
  • Once on day 1
  • High-risk disease only: once on day 3
• Methotrexate (MTX) 12 mg intrathecal once on day 1 (admixed with Cytarabine and Hydrocortisone (Cortef) 50 mg)

Supportive medications

• Folinic acid (Leucovorin) as follows:
  • 200 mg/m² IV once 24 hours after Methotrexate (MTX), then
  • 25 mg/m² IV every 6 hours until methotrexate level is <50 nmol/L
• Pegfilgrastim (Neulasta) 6 mg SC once on day 3
• Filgrastim (Neupogen) (dose not specified) SC once per day, starting once methotrexate level is <50 nmol/L (approximately day 18) and continuing until ANC >1,000/uL

Regimen B: R-IVAC

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Ifosfamide (Ifex) 1500 mg/m²/day IV continuous infusion on days 1 to 5
• Etoposide (Vepesid) 60 mg/m²/day IV continuous infusion on days 1 to 5
• Cytarabine (Cytosar) 2000 mg/m² IV every 12 hours on days 1 & 2 (total of 4 doses per cycle)

CNS prophylaxis

• Methotrexate (MTX) 12 mg intrathecal once on day 5

Supportive medications

• Mesna (Mesnex) 1500 mg/m²/day IV continuous infusion on days 1 to 5
• Pegfilgrastim (Neulasta) 6 mg SC once on day 6

Low-risk patients received 3 cycles of regimen A (R-CODOX-M); high-risk patients received 4 alternating cycles (A -> B -> A -> B)

References

1. Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. link to original article contains verified protocol PubMed
2. Retrospective: Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. link to original article contains partial protocol PubMed content property of HemOnc.org
3. Retrospective: Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. link to original article PubMed
4. Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. link to original article link to PMC article contains verified protocol PubMed

R-EPOCH, dose-escalated (EPOCH-R)

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R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Regimen

Study	Evidence	Comparator
Sparano et al. 2010 (AMC034)	Randomized Phase II	EPOCH -> R

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once "before each EPOCH cycle"
• Etoposide (Vepesid) 50 mg/m²/day IV continuous infusion on days 1 to 4 (total dose of 200 mg/m2)
• Prednisone (Sterapred) 60 mg/m² PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion on days 1 to 4 (total dose of 1.6 mg/m2)
• Cyclophosphamide (Cytoxan) as follows:
  • CD4 count <100/uL: 187 mg/m² IV over 15 minutes once on day 5
  • CD4 count >100/uL: 375 mg/m² IV over 15 minutes once on day 5
  • In each subsequent cycle, increase dose of Cyclophosphamide (Cytoxan) by 187 mg/m² if the neutrophil nadir is >500/µL and platelet nadir is >25/µL. Decrease dose of Cyclophosphamide (Cytoxan) by 187 mg/m² if the neutrophil nadir is <500/µL or platelet nadir is <25/µL.
• Doxorubicin (Adriamycin) 10 mg/m²/day IV continuous infusion on days 1 to 4 (total dose of 40 mg/m2)

Supportive medications

• EITHER Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"—no absolute count specified
• OR Pegfilgrastim (Neulasta) 6 mg SC x1 24 hours after EPOCH is completed
• Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
• Fluconazole (Diflucan) 100 mg PO once per day
• Ciprofloxacin (Cipro) 500 mg PO BID, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000
  • Other fluoroquinolone can be used at discretion of physician

21-day cycle for 6 to 8 cycles

References

1. Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. link to original article contains verified protocol PubMed

SC-EPOCH-RR

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SC-EPOCH-RR: Short Course Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin, with dose-dense Rituximab

Regimen

Study	Evidence
Dunleavy et al. 2010	Phase II
Dunleavy et al. 2013	Phase II, <20 pts in this arm

Dunleavy et al. 2010 reports on HIV+ DLBCL patients, whereas Dunleavy et al. 2013 reports on HIV+ Burkitt lymphoma patients. The regimen is the same.

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV over 3 hours once per day on days 1 & 5
• Etoposide (Vepesid) 50 mg/m²/day IV continuous infusion on days 1 to 4 (total dose of 200 mg/m2)
• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion on days 1 to 4 (total dose of 1.6 mg/m2)
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 2 hours once on day 5
• Doxorubicin (Adriamycin) 10 mg/m²/day IV continuous infusion on days 1 to 4 (total dose of 40 mg/m2)

Dose modifications:

• Cyclophosphamide (Cytoxan)
  • In the subsequent cycle, decrease dose of Cyclophosphamide (Cytoxan) by 187 mg/m² if ANC was less than 500/mm3 for 2 to 4 days or platelets were less than 25k for 2 to 4 days.
  • In the subsequent cycle, decrease dose of Cyclophosphamide (Cytoxan) by 375 mg/m² if ANC was less than 500/mm3 for 5 or more days or platelets were less than 25k for 5 or more days.
  • If Cyclophosphamide (Cytoxan) was dose-reduced in prior cycle, increase dose of by 187 mg/m2, up to maximum of 750 mg/m2, if ANC was > 500/mm3 and platelets were > 25k for the entire cycle.

CNS prophylaxis

• Methotrexate (MTX) 12 mg IT once per day on days 1 & 5 of cycles 3 to 5 (6 total doses)

Supportive medications

• Filgrastim (Neupogen) 300 mcg SC once per day starting on day 6, continue until ANC > 5k/ul above nadir
• Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
• Omeprazole (Prilosec) 20 mg PO once per day (or equivalent)
• Docusate (Colace) and Sennosides (Senna 2 tablets PO BID as necessary for constipation
• Lactulose 20 gms PO Q6H as necessary for constipation.

21-day cycles for one cycle beyond CR, minimum 3 and maximum of 6 cycles

References

1. Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, Steinberg SM, Yarchoan R, Jaffe ES, Wilson WH. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010 Apr 15;115(15):3017-24. Epub 2010 Feb 3. link to original article contains verified protocol PubMed
2. Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. link to original article contains verified protocol PubMed