Follicular lymphoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? Please go to the main follicular lymphoma regimen page to find other regimens.

30 regimens on this page
38 variants on this page


Note: Some of these regimens are not specific to follicular lymphoma because they were published before the modern classification schema was finalized. That said, most indolent lymphomas are follicular lymphoma and unless otherwise specified these should be assumed to be germane to follicular lymphoma.

First-line therapy

CHOP

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

Regimen variant #1, capped vincristine

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Nickenig et al. 2006 (GLSG '96) 1996-1998 Phase 3 (E-switch-ic) MCP Might have superior CR rate
Hiddemann et al. 2005 (GLSG '00) 2000-2003 Phase 3 (C) R-CHOP Inferior OS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles


Regimen variant #2, uncapped vincristine

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Zinzani et al. 2004 1999-2002 Phase 3 (C) FM Inferior CR rate

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles

Subsequent treatment

  • Zinzani et al. 2004, patients with PR or CR with detectable bcl-2/IgH fusion by PCR: R consolidation x 4

References

  1. Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. link to original article contains dosing details in manuscript PubMed
  2. GLSG '00: Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. link to original article contains dosing details in manuscript PubMed
  3. GELA GELF-94: Sebban C, Mounier N, Brousse N, Belanger C, Brice P, Haioun C, Tilly H, Feugier P, Bouabdallah R, Doyen C, Salles G, Coiffier B. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 2006 Oct 15;108(8):2540-4. Epub 2006 Jul 11. link to original article PubMed NCT00140569
  4. GLSG '96: Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. link to original article contains dosing details in manuscript PubMed

CHOP-B

CHOP-B: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Bleomycin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Peterson et al. 2003 (CALGB 7951) 1980-1985 Phase 3 (E-esc) Cyclophosphamide Did not meet primary endpoint of OS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles, then 28-day cycles up to 2 years beyond maximal response

References

  1. CALGB 7951: Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. link to original article contains dosing details in manuscript PubMed

CHOP, then 131Iodine-Tositumomab

CHOP-RIT: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne RadioImmunoTherapy

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Press et al. 2003 (SWOG S9911) 1999-2000 Phase 2
Press et al. 2012 (SWOG S0016) 2001-2008 Phase 3 (E-switch-ooc) R-CHOP Superior PFS1 (co-primary endpoint)

1Reported efficacy for SWOG S0016 is based on the 2018 update.

Induction

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 cycles, followed by:


Consolidation

Radioconjugate therapy, dosimetric step

  • On Day 1, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Supportive therapy

Radioconjugate therapy, therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive therapy

References

  1. SWOG S9911: Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, Gaynor ER, Rivkin SE, Fisher RI. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003 Sep 1;102(5):1606-12. Epub 2003 May 8. link to original article contains dosing details in manuscript PubMed NCT00003784
    1. Update: Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; SWOG. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. link to original article PubMed
  2. SWOG S0016: Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. link to original article contains partial protocol link to PMC article PubMed NCT00006721
    1. Update: Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. link to original article link to PMC article PubMed

CHVP

CHVP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Solal-Celigny et al. 1993 (GELA GELF-86) 1986-1991 Phase 3 (C) CHVP-I Seems to have inferior OS

Chemotherapy

Glucocorticoid therapy

1-month cycle for 6 cycles

Subsequent treatment

  • GELA GELF-86, SD or better: CHVP maintenance

References

  1. GELA GELF-86: Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, Coiffier B, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med. 1993 Nov 25;329(22):1608-14. link to original article contains dosing details in manuscript PubMed

CHVP-I

CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone, Interferon alfa-2b

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Solal-Celigny et al. 1993 (GELA GELF-86) 1986-1991 Phase 3 (E-RT-esc) CHVP Seems to have superior OS
Deconinck et al. 2005 (GOELAMS 064) 1994-2001 Phase 3 (C) VCAP, then HDT Seems to have inferior EFS

Chemotherapy

Glucocorticoid therapy

Immunotherapy

1-month cycle for 6 cycles, then 2-month cycle for 6 cycles

References

  1. GELA GELF-86: Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, Coiffier B, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med. 1993 Nov 25;329(22):1608-14. link to original article contains dosing details in manuscript PubMed
  2. GOELAMS 064: Deconinck E, Foussard C, Milpied N, Bertrand P, Michenet P, Cornillet-LeFebvre P, Escoffre-Barbe M, Maisonneuve H, Delwail V, Gressin R, Legouffe E, Vilque JP, Desablens B, Jaubert J, Ramee JF, Jenabian A, Thyss A, Le Pourhiet-Le Mevel A, Travade P, Delepine R, Colombat P; GOELAMS. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS. Blood. 2005 May 15;105(10):3817-23. Epub 2005 Feb 1. link to original article contains dosing details in manuscript PubMed NCT00696735
    1. Update: Gyan E, Foussard C, Bertrand P, Michenet P, Le Gouill S, Berthou C, Maisonneuve H, Delwail V, Gressin R, Quittet P, Vilque JP, Desablens B, Jaubert J, Ramée JF, Arakelyan N, Thyss A, Moluçon-Chabrot C, Delépine R, Milpied N, Colombat P, Deconinck E; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS). High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood. 2009 Jan 29;113(5):995-1001. Epub 2008 Oct 27. link to original article PubMed

CHVP-I (Etoposide)

CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), VP-16 (Etoposide), Prednisolone, Interferon alfa-2a

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Salles et al. 2008 (FL2000) 2000-2002 Phase 3 (C) R-CHVP+I Inferior EFS (primary endpoint)

Note: Interferon was continued for a full 18 months. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Glucocorticoid therapy

Immunotherapy

  • Interferon alfa-2a (Roferon-A) by the following age-based criteria:
    • Younger than 70 years old: 4,500,000 units SC three times per week
    • Older than 70 years old: 3,000,000 units SC three times per week

28-day cycle for 6 cycles, then 56-day cycle for 6 cycles (see note)

References

  1. FL2000: Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. link to original article contains dosing details in manuscript PubMed NCT00136552
    1. Update: Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. link to original article link to PMC article PubMed

CHVP-I (Prednisolone)

CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisolone, Interferon alfa-2b

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sebban et al. 2006 (GELA GELF-94) 1994-2001 Phase 3 (C) CHOP, then HDT Did not meet primary endpoint of EFS

Chemotherapy

Glucocorticoid therapy

Immunotherapy

1-month cycle for 6 cycles, then 2-month cycle for 6 cycles

References

  1. GELA GELF-94: Sebban C, Mounier N, Brousse N, Belanger C, Brice P, Haioun C, Tilly H, Feugier P, Bouabdallah R, Doyen C, Salles G, Coiffier B. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 2006 Oct 15;108(8):2540-4. Epub 2006 Jul 11. link to original article PubMed NCT00140569

COPA

COPA: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Adriamycin (Doxorubicin)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
O'Connell et al. 1987 1978-1983 Phase 3 (C) 1. COPA-B
2. CAP-BOP 		Did not meet efficacy endpoints
Smalley et al. 1992 (ECOG E6484) 1985-1988 Phase 3 (C) I-COPA Inferior TTTF

Note: this regimen is very similar but distinct from CHOP. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Glucocorticoid therapy

28-day cycle for 8 cycles

References

  1. O'Connell MJ, Harrington DP, Earle JD, Johnson GJ, Glick JH, Carbone PP, Creech RH, Neiman RS, Mann RB, Silverstein MN; ECOG. Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma. J Clin Oncol. 1987 Sep;5(9):1329-39. link to original article PubMed
  2. ECOG E6484: Smalley RV, Andersen JW, Hawkins MJ, Bhide V, O'Connell MJ, Oken MM, Borden EC. Interferon alfa combined with cytotoxic chemotherapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1336-41. link to original article contains dosing details in manuscript PubMed

CVP

CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
VCP: Vincristine, Cyclophosphamide, Prednisone

Regimen variant #1, 750/1.4/40

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Hagenbeek et al. 2006 1993-1997 Phase 3 (C) Fludarabine Did not meet primary endpoint of PFS48 Less toxic
Marcus et al. 2004 (M39021) 2000-2002 Phase 3 (C) R-CVP Inferior TTP Similar toxicity

Chemotherapy

Glucocorticoid therapy

21-day cycle for up to 8 cycles


Regimen variant #2, 1000/1.4/100

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hochster et al. 2009 (ECOG E1496) NR Phase 3 (C) FC Not reported

Note: the FC arm was closed prematurely and comparisons between CVP and FC were not conducted.

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles

Subsequent treatment


Regimen variant #3, 2000/1.4/100

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Unterhalt et al. 1996 1989-04 to 1996-01 Phase 3 (C) PmM Seems to have inferior EFS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles

Subsequent treatment

References

  1. Unterhalt M, Herrmann R, Tiemann M, Parwaresch R, Stein H, Trümper L, Nahler M, Reuss-Borst M, Tirier C, Neubauer A, Freund M, Kreuser ED, Dietzfelbinger H, Bodenstein H, Engert A, Stauder R, Eimermacher H, Landys K, Hiddemann W; German Low-Grade Lymphoma Study Group. Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. Leukemia. 1996 May;10(5):836-43. PubMed
    1. Update: Hiddemann W, Unterhalt M, Herrmann R, Wöltjen HH, Kreuser ED, Trümper L, Reuss-Borst M, Terhardt-Kasten E, Busch M, Neubauer A, Kaiser U, Hanrath RD, Middeke H, Helm G, Freund M, Stein H, Tiemann M, Parwaresch R. Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol. 1998 May;16(5):1922-30. link to original article PubMed
  2. M39021: Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. Epub 2004 Oct 19.link to original article contains dosing details in abstract PubMed
    1. Update: Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. link to original article PubMed
  3. Hagenbeek A, Eghbali H, Monfardini S, Vitolo U, Hoskin PJ, de Wolf-Peeters C, MacLennan K, Staab-Renner E, Kalmus J, Schott A, Teodorovic I, Negrouk A, van Glabbeke M, Marcus R. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol. 2006 Apr 1;24(10):1590-6. link to original article contains dosing details in abstract PubMed
  4. ECOG E1496: 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00003204
    1. Update: Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. link to original article link to PMC article PubMed

CVP, then 131Iodine-Tositumomab

CVP-RIT: Cyclophosphamide, Vincristine, Prednisone, then RadioImmunoTherapy

Study Evidence
Link et al. 2010 Phase 2

Induction

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles, followed within 56 days by:


Consolidation

Radioconjugate therapy, dosimetric step

  • On Day 1, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Supportive therapy, dosimetric step

Radioconjugate therapy, therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive therapy, therapeutic step

References

  1. Link BK, Martin P, Kaminski MS, Goldsmith SJ, Coleman M, Leonard JP. Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study. J Clin Oncol. 2010 Jun 20;28(18):3035-41. Epub 2010 May 10. link to original article PubMed.

Fludarabine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Zinzani et al. 2000 1995-1998 Phase 3 (C) Fludarabine & Idarubicin Superior CR rate1

1The superiority of this arm was only observed in the FL subgroup; overall, there was no statistically significant difference between arms.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

28-day cycle for 6 cycles

References

  1. Zinzani PL, Magagnoli M, Moretti L, De Renzo A, Battista R, Zaccaria A, Guardigni L, Mazza P, Marra R, Ronconi F, Lauta VM, Bendandi M, Gherlinzoni F, Gentilini P, Ciccone F, Cellini C, Stefoni V, Ricciuti F, Gobbi M, Tura S. Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma. J Clin Oncol. 2000 Feb;18(4):773-9. link to original article contains dosing details in manuscript PubMed

Cyclophosphamide & Fludarabine (FC)

FC: Fludarabine & Cyclophosphamide
CF: Cyclophosphamide & Fludarabine

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hochster et al. 2009 (ECOG E1496) NR Phase 3 (E-switch-ic) CVP Not reported

Note: investigation into this regimen was halted due to excess mortality.

Chemotherapy

28-day cycle for up to 8 cycles

Subsequent treatment

References

  1. ECOG E1496: 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. link to original article contains dosing details in manuscript PubMed

Fludarabine, then 131Iodine-Tositumomab

Study Evidence
Leonard et al. 2005 Phase 2

Induction

Chemotherapy

35-day cycle for 3 cycles, followed by:


Consolidation

Radioconjugate therapy, dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Radioconjugate therapy, therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

  1. Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005 Aug 20;23(24):5696-704. link to original article contains dosing details in manuscript PubMed

FM

FM: Fludarabine, Mitoxantrone

Regimen variant #1, 75/10, IV fludarabine

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Zinzani et al. 2004 1999-2002 Phase 3 (E-switch-ic) CHOP Superior CR rate (primary endpoint)

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

  • Zinzani et al. 2004, patients with PR or CR with detectable bcl-2/IgH fusion by PCR: R consolidation x 4


Regimen variant #2, 100/10, IV fludarabine

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Foussard et al. 2005 1995-1999 Phase 3 (E-switch-ic) mini-CHVP Superior FFS

Chemotherapy

28-day cycle for 6 cycles

Subsequent treatment

  • FM consolidation


Regimen variant #3, 120/10, PO fludarabine

Study Evidence Efficacy
Zinzani et al. 2008 (FLUMIZ) Phase 2 ORR: 98%

Chemotherapy

Supportive therapy

28-day cycle for 6 cycles

Subsequent treatment

  • Patients were restaged 4 to 6 weeks after finishing cycle 6.
  • FLUMIZ, at least a partial response (PR), ANC greater than 1500/μL, platelet count greater than 100 x 109/L, and less than 25% bone marrow involvement were eligible for: ibritumomab tiuxetan consolidation, 6 to 10 weeks after the end of cycle 6.

Dose and schedule modifications

  • G-CSF could be used for later cycles at physician discretion if grade 3 or 4 neutropenia or delayed neutropenic fever occurred.

References

  1. Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. link to original article contains dosing details in manuscript PubMed
  2. Foussard C, Colombat P, Maisonneuve H, Berthou C, Gressin R, Rousselet MC, Rachieru P, Pignon B, Mahé B, Ghandour C, Desablens B, Casassus P, Lamy T, Delwail V, Deconinck E; GOELAMS. Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies. Ann Oncol. 2005 Mar;16(3):466-72. Epub 2005 Feb 2. link to original article contains dosing details in abstract PubMed
  3. FLUMIZ: Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. link to original article contains dosing details in manuscript PubMed EudraCT 2004-002211-92

FND

FND: Fludarabine, Novantrone (Mitoxantrone), Dexamethasone

Regimen

Study Dates of enrollment Evidence
McLaughlin et al. 1996 1992-01 to 1993-12 Phase 2

Chemotherapy

Glucocorticoid therapy

28-day cycle for up to 8 cycles

References

  1. McLaughlin P, Hagemeister FB, Romaguera JE, Sarris AH, Pate O, Younes A, Swan F, Keating M, Cabanillas F. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol. 1996 Apr;14(4):1262-8. link to original article contains dosing details in manuscript PubMed

131Iodine-Tositumomab monotherapy

Regimen

Study Dates of enrollment Evidence
Kaminski et al. 2005 1996-06 to 1999-04 Phase 2

Note: Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Radioconjugate therapy, dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Radioconjugate therapy, therapeutic step

  • Tositumomab 450 mg IV over 60 minutes on any day from 7 to 14
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 as follows:
    • Platelet count 150 x 109/L or more: A dose that will provide 75 cGy of radiation to the total body IV over 20 minutes on any day from 7 to 14
    • Platelet count 100 x 109/L to 150 x 109/L: A dose that will provide 65 cGy of radiation to the total body IV over 20 minutes on any day from 7 to 14

One course

References

  1. Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9. link to original article contains dosing details in manuscript PubMed
    1. Update: Abstract: Mark S. Kaminski, MD, Melissa Tuck, MS, Judith Estes, BSN, MSN, Arne Kolstad, MD, PhD, Charles Warren Ross, MD, Denise Regan, BS, Thierry Horner, PhD, Vanessa C. Williams, MS, Tina Vleisides, DC and Richard L. Wahl, MD. Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma: Median 10 Year Follow-up Results. ASH 2009 abstract 3759.

MCP

MCP: Mitoxantrone, Chlorambucil, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Nickenig et al. 2006 (GLSG '96) 1996-1998 Phase 3 (E-switch-ic) CHOP Might have inferior CR rate

Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2.

Chemotherapy

Glucocorticoid therapy

28-day cycle for 6 to 8 cycles

References

  1. GLSG '96: Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. link to original article contains dosing details in manuscript PubMed

MCP (Prednisolone)

MCP: Mitoxantrone, Chlorambucil, Prednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Herold et al. 2007 (OSHO-39) 1998-2003 Phase 3 (C) R-MCP Inferior OS

Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2.

Chemotherapy

Glucocorticoid therapy

28-day cycle for up to 8 cycles

Subsequent treatment

  • OSHO-39, patients who achieved a PR or CR: Interferon alfa-2a maintenance, within 4 to 8 weeks of completion of chemotherapy

References

  1. OSHO-39: Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. link to original article contains dosing details in manuscript PubMed NCT00269113
    1. Update: Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. link to original article PubMed

ProMACE-MOPP

ProMACE-MOPP: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study Evidence Comparator
Young et al. 1988 Phase 3 (E-esc) Observation

Chemotherapy

Glucocorticoid therapy

References

  1. Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. PubMed

Consolidation after first-line therapy

131Iodine-Tositumomab monotherapy

Regimen

Study Dates of enrollment Evidence
Friedberg et al. 2014 (SWOG S0433) 2005-11 to 2010-03 Phase 2

Will be added if drug is ever returned to market.

Preceding treatment

Radioconjugate therapy

References

  1. SWOG S0433: Friedberg JW, Unger JM, Burack WR, Gopal AK, Raju RN, Nademanee AP, Kaminski MS, Li H, Press OW, Miller TP, Fisher RI. R-CHOP with iodine-131 tositumomab consolidation for advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0433. Br J Haematol. 2014 Aug;166(3):382-9. Epub 2014 Apr 18. link to original article link to PMC article does not contain dosing details PubMed NCT00107380

Maintenance after first-line therapy

Interferon alfa-2a monotherapy

Regimen variant #1, 3 MU TIW

Study Dates of enrollment Evidence
Salles et al. 2008 (FL2000) 2000-2002 Non-randomized part of phase 3 RCT

Note: This variant was intended for patients older than 70 years.

Preceding treatment

Immunotherapy

7-day cycle for 78 cycles (18 months)


Regimen variant #2, 4.5 MU TIW x 18 mo

Study Dates of enrollment Evidence
Salles et al. 2008 (FL2000) 2000-2002 Non-randomized part of phase 3 RCT

Note: This variant was intended for patients younger than 70 years.

Preceding treatment

Immunotherapy

7-day cycle for 78 cycles (18 months)


Regimen variant #3, 4.5 MU TIW, indefinitely

Study Dates of enrollment Evidence
Herold et al. 2007 (OSHO-39) 1998-2003 Non-randomized part of phase 3 RCT

Preceding treatment

Immunotherapy

7-day cycles


Regimen variant #4, 5 MU TIW

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lenz et al. 2004 1996-2000 Phase 3 (C) Cy/TBI, then auto HSCT Inferior PFS

Preceding treatment

Immunotherapy

7-day cycles

References

  1. Lenz G, Dreyling M, Schiegnitz E, Forstpointner R, Wandt H, Freund M, Hess G, Truemper L, Diehl V, Kropff M, Kneba M, Schmitz N, Metzner B, Pfirrmann M, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 1;104(9):2667-74. Epub 2004 Jul 6. link to original article contains dosing details in manuscript PubMed
  2. OSHO-39: Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. link to original article contains dosing details in manuscript PubMed NCT00269113
  3. FL2000: Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. link to original article contains dosing details in manuscript PubMed NCT00136552
    1. Update: Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. link to original article link to PMC article PubMed

Relapsed or refractory

CHOP

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Van Oers et al. 2006 (EORTC 20981) 1998-2004 Phase 3 (C) R-CHOP Might have inferior OS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles

Subsequent treatment

References

  1. EORTC 20981: van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains dosing details in manuscript PubMed NCT00004179
    1. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains dosing details in manuscript link to PMC article PubMed

FCM

FCM: Fludarabine, Cyclophosphamide, Mitoxantrone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Forstpointner et al. 2004 1998-2001 Phase 3 (C) R-FCM Seems to have inferior PFS

Chemotherapy

28-day cycle for 4 cycles

Subsequent treatment

References

  1. Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains dosing details in manuscript PubMed
    1. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains dosing details in manuscript PubMed

Fludarabine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Klasa et al. 2002 1993-1996 Phase 3 (E-switch-ic) CVP Seems to have superior PFS

Chemotherapy

28-day cycles

References

  1. Klasa RJ, Meyer RM, Shustik C, Sawka CA, Smith A, Guévin R, Maksymiuk A, Rubinger M, Samosh M, Laplante S, Grenier JF. Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen. J Clin Oncol. 2002 Dec 15;20(24):4649-54. link to original article contains dosing details in manuscript PubMed

FMP

FMP: Fludarabine, Mitoxantrone, Prednisone

Regimen

Study Evidence
Zinzani et al. 1995a Phase 2

Chemotherapy

Glucocorticoid therapy

References

  1. Zinzani PL, Bendandi M, Tura S. FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):262-6. link to original article contains dosing details in abstract PubMed

Fludarabine & Rituximab (FR)

FR: Fludarabine & Rituximab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Rummel et al. 2015 (StiL NHL 2-2003) 2003-2010 Phase 3 (C) BR Inferior PFS

Chemotherapy

Targeted therapy

28-day cycle for up to 6 cycles

References

  1. StiL NHL 2-2003: Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. link to original article contains dosing details in abstract PubMed NCT01456351

Idelalisib monotherapy

Regimen

Study Dates of enrollment Evidence
Gopal et al. 2014 (DELTA) 2011-2012 Phase 2 (RT)

Targeted therapy

Continued indefinitely

References

  1. DELTA: Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01282424
    1. Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. link to abstract

Interferon alfa monotherapy

Regimen

Study Evidence
Foon et al. 1984 Phase 2

Immunotherapy

References

  1. Foon KA, Sherwin SA, Abrams PG, Longo DL, Fer MF, Stevenson HC, Ochs JJ, Bottino GC, Schoenberger CS, Zeffren J, Jaffe ES, Oldham RK. Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A interferon. N Engl J Med. 1984 Nov 1;311(18):1148-52. link to original article PubMed

131Iodine-Tositumomab monotherapy

Regimen

Study Dates of enrollment Evidence
Kaminski et al. 1993 NR Non-randomized, fewer than 20 pts
Press et al. 1995 NR Phase 2
Kaminski et al. 2001 (RIT-II-004) 1996-1998 Phase 2 (RT)
Horning et al. 2004 (CP-97-012) 1998-1999 Phase 2 (RT)
Olney et al. 2014 (SB-393229/032) 2004-2007 Phase 2

Note: Kiminski et al. 1993 and Press et al. 1995 are included here for historic context but had different treatment details.

Radioconjugate therapy, dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Radioconjugate therapy, therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive therapy, therapeutic step

References

  1. Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD, Crawford SM, Burgess JM, Petry NA, Butchko GM, Glenn SD, Wahl RL. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993 Aug 12;329(7):459-65. link to original article PubMed
  2. Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S, Fisher DR, Porter B, Matthews DC, Gooley T, Bernstein ID. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet. 1995 Aug 5;346(8971):336-40. link to original article PubMed
  3. RIT-II-004: Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. link to original article contains dosing details in manuscript PubMed
  4. CP-97-012: Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005 Feb 1;23(4):712-9. Epub 2004 Dec 21. link to original article PubMed
  5. Meta-analysis: Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. link to original article PubMed
  6. SB-393229/032: Olney HJ, Freeman MA, Stewart DA, Mangel JE, White DJ, Elia-Pacitti JO. Prolonged progression-free survival and preserved quality of life in the Canadian prospective study of tositumomab and iodine(131)-tositumomab for previously treated, rituximab-exposed, indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2014 Dec;55(12):2754-60. Epub 2014 Apr 3. link to original article PubMed NCT00240565

Ofatumumab monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hagenbeek et al. 2008 (Hx-CD20-001) 2004-2005 Phase 1/2
Czucman et al. 2012 (405 Study) 2006-2008 Phase 2
Maloney et al. 2020 (HOMER) 2010-2016 Phase 3 (E-switch-ic) Rituximab Did not meet primary endpoint of PFS

Note: there was no MTD determined in Hx-CD20-001.

Targeted therapy

  • Ofatumumab (Arzerra) as follows:
    • Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
    • Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22

Supportive therapy

28-day cycle for 2 cycles

References

  1. Hx-CD20-001: Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, Link BK, Robak T, Wojtukiewicz M, Pfreundschuh M, Kneba M, Engert A, Sonneveld P, Flensburg M, Petersen J, Losic N, Radford J. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008 Jun 15;111(12):5486-95. Epub 2008 Apr 4. link to original article PubMed NCT00092274
  2. 405 Study: Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00394836
  3. HOMER: Maloney DG, Ogura M, Fukuhara N, Davis J, Lasher J, Izquierdo M, Banerjee H, Tobinai K. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 2020 Aug 25;4(16):3886-3893. link to original article link to PMC article PubMed NCT01200589

Umbralisib monotherapy

Regimen

Study Dates of enrollment Evidence
Fowler et al. 2021 (UNITY-NHL) 2017-2018 Phase 2b (RT)

Targeted therapy

28-day cycles

References

  1. UNITY-NHL: Fowler NH, Samaniego F, Jurczak W, Ghosh N, Derenzini E, Reeves JA, Knopińska-Posłuszny W, Cheah CY, Phillips T, Lech-Maranda E, Cheson BD, Caimi PF, Grosicki S, Leslie LA, Chavez JC, Fonseca G, Babu S, Hodson DJ, Shao SH, Burke JM, Sharman JP, Law JY, Pagel JM, Miskin HP, Sportelli P, O'Connor OA, Weiss MS, Zinzani PL. Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2021 May 20;39(15):1609-1618. Epub 2021 Mar 8. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02793583
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