Burkitt lymphoma

From HemOnc.org - A Hematology Oncology Wiki
Jump to: navigation, search
Section editor
Jcvillasboas.jpg
J.C. Villasboas Bisneto, MD
Mayo Clinic
Rochester, MN
20 regimens on this page
25 variants on this page

Note 1: Regimens specifically intended for HIV-related Burkitt lymphoma can be found on the HIV-associated lymphoma page.

Note 2: The regimens on this page are primarily intended for the sporadic form of Burkitt lymphoma and some other high-grade B-cell lymphomas. In the future we plan to add regimens for the endemic form of Burkitt lymphoma.

Contents


Untreated, pre-phase

COP

back to top

COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Diviné et al. 2005 (LMB95) Phase II
Ribrag et al. 2016 (LMBA-02) Non-randomized portion of RCT

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement).

Chemotherapy

CNS prophylaxis (group B)

CNS treatment (group C)

One cycle

Subsequent treatment

References

  1. LMB95: Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed
  2. Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Jun 11;387(10036):2402-11. Epub 2016 Apr 11. link to original article contains verified protocol PubMed

Cyclophosphamide & Prednisone

back to top

Variant #1, 1000/300

Study Evidence
Oriol et al. 2008 Non-randomized
Hoelzer et al. 2014 (GMALL-B-ALL/NHL 2002) Non-randomized

Note: GMALL-B-ALL/NHL 2002 is fairly similar to the GMALL-R regimen, with some minor differences. See text for details.

Chemotherapy

CNS prophylaxis

One cycle

Subsequent treatment

  • Oriol et al. 2008: PETHEMA induction; see text for details
  • GMALL-B-ALL/NHL 2002: Induction; see text for details

Variant #2, 1000/420

Study Evidence
Lee et al. 2001 (CALGB 9251) Non-randomized
Rizzieri et al. 2014 (CALGB 10-002) Phase II

CALGB 9251 is an earlier version of CALGB 10-002 that demonstrated that cranial radiation can be omitted in the treatment of Burkitt lymphoma.

Chemotherapy

Supportive medications

Subsequent treatment

References

  1. CALGB 9251: Lee EJ, Petroni GR, Schiffer CA, Freter CE, Johnson JL, Barcos M, Frizzera G, Bloomfield CD, Peterson BA. Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of Cancer and Leukemia Group B study 9251. J Clin Oncol. 2001 Oct 15;19(20):4014-22. link to original article PubMed
    1. Update: Rizzieri DA, Johnson JL, Niedzwiecki D, Lee EJ, Vardiman JW, Powell BL, Barcos M, Bloomfield CD, Schiffer CA, Peterson BA, Canellos GP, Larson RA. Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer. 2004 Apr 1;100(7):1438-48. link to original article PubMed
  2. Oriol A, Ribera JM, Bergua J, Giménez Mesa E, Grande C, Esteve J, Brunet S, Moreno MJ, Escoda L, Hernandez-Rivas JM, Hoelzer D; PETHEMA. High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients. Cancer. 2008 Jul 1;113(1):117-25. link to original article contains verified protocol PubMed
  3. CALGB 10-002: Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. Epub 2014 Jan 15. link to original article contains verified protocol link to PMC article PubMed
  4. GMALL-B-ALL/NHL 2002: Hoelzer D, Walewski J, Döhner H, Viardot A, Hiddemann W, Spiekermann K, Serve H, Dührsen U, Hüttmann A, Thiel E, Dengler J, Kneba M, Schaich M, Schmidt-Wolf IG, Beck J, Hertenstein B, Reichle A, Domanska-Czyz K, Fietkau R, Horst HA, Rieder H, Schwartz S, Burmeister T, Gökbuget N; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014 Dec 18;124(26):3870-9. Epub 2014 Oct 30. link to original article contains verified protocol link to PMC article PubMed

Untreated

BASIC

back to top

BASIC: Brief, Anthracycline-Sparing, Intensive Cyclophosphamide

Regimen

Study Evidence
Kasamon et al. 2012 (J0409) Non-randomized

Chemotherapy

Supportive medications

CNS prophylaxis

14-day cycle for 2 cycles

Subsequent treatment

References

  1. J0409: Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. link to original article contains verified protocol link to PMC article PubMed

CALGB 10-002 regimen

back to top

Regimen

Study Evidence
Rizzieri et al. 2014 (CALGB 10-002) Phase II

Preceding treatment

Chemotherapy, cycles 2, 4, 6

CNS prophylaxis

Supportive medications

21-day cycles

Chemotherapy, cycles 3, 5, 7

CNS prophylaxis

Supportive medications

21-day cycles

References

  1. CALGB 10-002: Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. Epub 2014 Jan 15. link to original article contains verified protocol link to PMC article PubMed

CODOX-M

back to top

CODOX-M: Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate

Variant #1, "Original Magrath"

Study Evidence
Magrath et al. 1996 (NCI 89-C-41) Phase II

This is intended for low-risk patients.

Chemotherapy

  • 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) as follows:
    • Age 65 years or younger: 300 mg/m2 IV over 60 minutes once on day 10, then 2700 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m2)
    • Age greater than 65 years: 100 mg/m2 IV over 60 minutes once on day 10, then 900 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m2)

Supportive medications

CNS prophylaxis

3 cycles

Variant #2, "Modified Magrath"

Study Evidence
LaCasce et al. 2004 Phase II, <20 pts

Note that dose reductions for age greater than 65 years were not described in this publication. This is intended for low-risk patients (i.e., single site of disease less than 10 cm with normal LDH).

Chemotherapy

CNS prophylaxis

Supportive medications

3 cycles

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. Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D; UKLG LY06 collaborators. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002 Aug;13(8):1264-74. Erratum in: Ann Oncol. 2002 Dec;13(12):1961. Norbert, P [corrected to Pescosta, N]. link to original article contains verified protocol PubMed
  3. 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
  4. 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 link to PMC article PubMed
  5. Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. link to original article contains verified protocol PubMed

CODOX-M/IVAC

back to top

CODOX-M/IVAC: Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate alternating with Ifosfamide, Vepesid (Etoposide), Ara-C (Cytarabine)

Variant #1, "Original Magrath"

Study Evidence
Magrath et al. 1996 (NCI 89-C-41) Phase II

This is intended for high-risk patients.

Chemotherapy, Part 1: CODOX-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 IV once per day on days 1 & 8
  • Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
  • Methotrexate (MTX) as follows:
    • Age 65 years or younger: 300 mg/m2 IV over 60 minutes once on day 10, then 2700 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m2)
    • Age greater than 65 years: 100 mg/m2 IV over 60 minutes once on day 10, then 900 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m2)

Supportive medications

CNS prophylaxis

Chemotherapy, Part 2: IVAC

  • Ifosfamide (Ifex) as follows:
    • Age 65 years or younger: 1500 mg/m2 IV over 60 minutes once per day on days 1 to 5
    • Age greater than 65 years: 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
  • Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 5
  • Cytarabine (Ara-C) as follows:
    • Age 65 years or younger: 2000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses)
    • Age greater than 65 years: 1000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses)

Supportive medications

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

CNS prophylaxis

2 cycles each of CODOX-M and IVAC (alternating)

Variant #2

Study Evidence
Mead et al. 2002 (UKLG LY06) Phase II

This is intended for high-risk patients; modifications to the original NCI 89-C-41 are only in the CODOX-M portion.

Chemotherapy, Part 1: CODOX-M

Supportive medications

CNS prophylaxis

Chemotherapy, Part 2: IVAC

  • Ifosfamide (Ifex) as follows:
    • Age 65 years or younger: 1500 mg/m2 IV over 60 minutes once per day on days 1 to 5
    • Age greater than 65 years: 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
  • Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 5
  • Cytarabine (Ara-C) as follows:
    • Age 65 years or younger: 2000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses)
    • Age greater than 65 years: 1000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses)

Supportive medications

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

CNS prophylaxis

2 cycles each of CODOX-M and IVAC (alternating)

Variant #3, "Modified Magrath"

Study Evidence
LaCasce et al. 2004 Phase II, <20 pts

All modifications are in Part 1: CODOX-M. Also note that dose reductions for age greater than 65 years were not described in this publication. This is intended for high-risk patients.

Chemotherapy, Part 1: CODOX-M

CNS prophylaxis

Supportive medications

Chemotherapy, Part 2: IVAC

CNS prophylaxis

Supportive medications

2 cycles each of CODOX-M and IVAC (alternating)

Variant #4

Study Evidence
Mead et al. 2008 (MRC/NCRI LY10) Phase II

This is intended for high-risk patients; modifications to the UKLG LY06 protocol are only in the CODOX-M portion.

Chemotherapy, Part 1: CODOX-M

Supportive medications

  • Folinic acid (Leucovorin) 15 mg/m2 IV once at 36 hours after start of IV Methotrexate (MTX), then 15 mg/m2 IV every 3 hours between hours 36 and 48, then 15 mg/m2 IV every 6 hours until MTX level less than 0.05
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL

CNS prophylaxis

Chemotherapy, Part 2: IVAC

  • Ifosfamide (Ifex) as follows:
    • Age 65 years or younger: 1500 mg/m2 IV over 60 minutes once per day on days 1 to 5
    • Age greater than 65 years: 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
  • Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 5
  • Cytarabine (Ara-C) as follows:
    • Age 65 years or younger: 2000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses)
    • Age greater than 65 years: 1000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (4 doses)

Supportive medications

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

CNS prophylaxis

2 cycles each of CODOX-M and IVAC (alternating)

References

  1. NCI 89-C-41: 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. UKLG LY06: Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D; UKLG LY06 collaborators. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002 Aug;13(8):1264-74. Erratum in: Ann Oncol. 2002 Dec;13(12):1961. Norbert, P [corrected to Pescosta, N]. link to original article contains verified protocol PubMed
  3. 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
  4. MRC/NCRI LY10: 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 link to PMC article PubMed
  5. Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. link to original article PubMed

COPAD

back to top

COPAD: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin)

Regimen

Study Evidence
Diviné et al. 2005 (LMB95) Phase II, <20 pts in this subgroup

This regimen is for group A (completely resected stage I or abdominal stage II disease).

Chemotherapy

3 cycles; intervals were as short as possible, as soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 109/L

References

  1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

COPADM

back to top

COPADM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study Evidence Comparator Comparative Efficacy
Diviné et al. 2005 (LMB95) Phase II
Ribrag et al. 2016 (LMBA-02) Phase III (C) R-COPADM Seems to have inferior EFS

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement). Diviné et al. 2005 list the dose of HD-MTX as 3 mg/m2 but this is presumed to be a typo.

Preceding treatment

Chemotherapy, COPADM #1

Supportive medications

CNS prophylaxis (group B)

CNS treatment (group C)

One cycle

As soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 109/L, patients proceeded to:

Chemotherapy, COPADM #2

Supportive medications

CNS prophylaxis (group B)

CNS treatment (group C)

One cycle

Subsequent treatment

References

  1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed
  2. Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Jun 11;387(10036):2402-11. Epub 2016 Apr 11. link to original article PubMed

DA-R-EPOCH

back to top

DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

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

Chemotherapy

Supportive medications

CNS prophylaxis

21-day cycle for 6 cycles if ANC greater than 1000/uL and platelets greater than 100 × 109/L

If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

Dose modifications

Note this is different than some other DA-EPOCH regimens!

  • Start cycle 1 as described above.
  • Obtain CBCs twice per week for nadir measurements.
  • If nadir ANC greater than or equal to 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • If nadir ANC less than 500/uL, use same doses as last cycle.
  • If nadir platelet count less than 25 × 109/L, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
    • Decreases below the cycle 1 starting dose only apply to cyclophosphamide, i.e., the lowest etoposide and doxorubicin would be dosed is at the original cycle 1 dose.

References

  1. 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 link to supplement contains verified protocol in supplement link to PMC article PubMed

GMALL-R

back to top

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.

Chemotherapy, prephase

Chemotherapy, cycle A

Supportive medications

Chemotherapy, cycle B

Supportive medications

Chemotherapy, cycle C

Supportive medications

Give regimen as follows:

  • Advanced stage and younger than 55 years: A->B->C for 2 courses (6 total cycles)
  • Older than 55 years: Alternate A & B for 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

8 doses total

References

  1. Burkimab: 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

R-CODOX-M

back to top

R-CODOX-M: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate

Regimen

Study Evidence
Maruyama et al. 2010 Pilot, <20 pts
Jacobson et al. 2014 Expert Recommendation

In the Jacobson et al. 2014 review, the authors describe a "Modified Magrath regimen of R-CODOX/R-IVAC" based on the timing and dosage of LaCasce et al. 2004. However, LaCasce et al. 2004 did not include rituximab in the schema. Others have published retrospective series of this regimen; doses here are based on the review article. This is for low-risk patients (i.e., single site of disease less than 10 cm with normal LDH).

Chemotherapy

CNS prophylaxis

CNS Treatment (for CSF positive)

Supportive medications

3 cycles

References

  1. Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. 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 PubMed
  3. Review: Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. 2014 Nov 6;124(19):2913-20. Epub 2014 Sep 25. link to original article contains verified protocol PubMed

R-CODOX-M/R-IVAC

back to top

R-CODOX-M/R-IVAC: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate alternating with Rituximab, Ifosfamide, Vepesid (etoposide), Ara-C (Cytarabine)

Regimen

Study Evidence
Jacobson et al. 2014 Expert Recommendation

In the Jacobson et al. 2014 review, the authors describe a "Modified Magrath regimen of R-CODOX/R-IVAC" based on the timing and dosage of LaCasce et al. 2004. However, LaCasce et al. 2004 did not include rituximab in the schema. Others have published retrospective series of this regimen; doses here are based on the review article. This is for high-risk patients.

Chemotherapy, Part 1: R-CODOX-M

CNS prophylaxis

CNS Treatment (for CSF positive)

Supportive medications

Chemotherapy, Part 2: R-IVAC

CNS prophylaxis

CNS Treatment (for CSF positive)

  • Treatment as per CNS prophylaxis PLUS in cycle 1 only:
  • Cytarabine (Ara-C) 50 mg IT once on day 3

Supportive medications

Patients receive 2 cycles each of R-CODOX-M and R-IVAC (alternating)

References

  1. Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. 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 PubMed
  3. Review: Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. 2014 Nov 6;124(19):2913-20. Epub 2014 Sep 25. link to original article contains verified protocol PubMed

R-CODOX-M (Doxil substituted)

back to top

R-CODOX-M: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXil (Pegylated liposomal doxorubicin), Methotrexate

Regimen

Study Evidence
Evens et al. 2013 Phase II

This regimen is for low-risk patients.

Chemotherapy

CNS prophylaxis

Supportive medications

3 cycles

References

  1. Evens AM, Carson KR, Kolesar J, Nabhan C, Helenowski I, Islam N, Jovanovic B, Barr PM, Caimi PF, Gregory SA, Gordon LI. A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Ann Oncol. 2013 Dec;24(12):3076-81. Epub 2013 Oct 20. link to original article contains verified protocol link to PMC article PubMed

R-CODOX-M/R-IVAC (Doxil substituted)

back to top

R-CODOX-M/R-IVAC: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXil (Pegylated liposomal doxorubicin), Methotrexate alternating with Rituximab, Ifosfamide, Vepesid (Etoposide), Ara-C (Cytarabine)

Regimen

Study Evidence
Evens et al. 2013 Phase II

This regimen is for high-risk patients.

Chemotherapy, Part 1: R-CODOX-M

CNS prophylaxis

Supportive medications

Chemotherapy, Part 2: R-IVAC

CNS prophylaxis

Supportive medications

Four alternating cycles of R-CODOX-M & R-IVAC

References

  1. Evens AM, Carson KR, Kolesar J, Nabhan C, Helenowski I, Islam N, Jovanovic B, Barr PM, Caimi PF, Gregory SA, Gordon LI. A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Ann Oncol. 2013 Dec;24(12):3076-81. Epub 2013 Oct 20. link to original article contains verified protocol link to PMC article PubMed

R-COPADM

back to top

R-COPADM: Rituximab, Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study Evidence Comparator Comparative Efficacy
Ribrag et al. 2016 (LMBA-02) Phase III (E) COPADM Seems to have superior EFS

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement); see manuscript for details about the regimen for group C.

Preceding treatment

Chemotherapy

Supportive medications

CNS prophylaxis

Two cycles

Subsequent treatment

References

  1. Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Jun 11;387(10036):2402-11. Epub 2016 Apr 11. link to original article PubMed

R-Hyper-CVAD/R-MA

back to top

R-Hyper-CVAD/R-MA: Rituximab, Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone altenating with Rituximab, Methotrexate, Ara-C (Cytarabine)

Regimen

Study Evidence
Thomas et al. 2006 Pilot, <20 pts

Chemotherapy, part A (cycles 1, 3, 5, 7)

CNS prophylaxis

Given each cycle for a total of 16 intrathecal treatments. If CNS disease present, therapy augmented to twice-weekly alternating (MTX, ara-C) treatments until CSF cell count normalizes and cytology is negative, then continues for 4 more alternating weekly treatments; prophylaxis course then resumes.

Supportive medications

Next cycle to start no sooner than 14 days or as soon as "unmaintained" WBC count is greater than 3 x 109/L and platelet count greater than 50 x 109/L

Dose modifications

  • Vincristine (Oncovin) reduced to 1 mg for bilirubin greater than 2 mg/dL or NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted for bilirubin greater than 3 mg/dL or for ileus
  • Doxorubicin (Adriamycin) reduced by 50% for bilirubin 2 to 3 mg/dL, by 75% for bilirubin 3 to 5 mg/dL (eliminated for bilirubin greater than 5 mg/dL or for gastric/small-bowel involvement with Course 1 to reduce duration of myelosuppression given risk of perforation)

Chemotherapy, part B (cycles 2, 4, 6, 8)

  • Rituximab (Rituxan) as follows:
    • Cycles 2 & 4: 375 mg/m2 IV over 2 to 6 hours once per day on days 2 & 8
  • Methotrexate (MTX) 1000 mg/m2 IV continuous infusion over 24 hours, started on day 1
  • Cytarabine (Ara-C) 3000 mg/m2 IV over 2 hours every 12 hours on days 2 & 3 (4 total doses)

CNS prophylaxis

Given each cycle for a total of 16 intrathecal treatments. If CNS disease present, therapy augmented to twice-weekly alternating (MTX, ara-C) treatments until CSF cell count normalizes and cytology is negative, then continues for 4 more alternating weekly treatments; prophylaxis course then resumes.

Supportive medications

Next cycle to start no sooner than 14 days or as soon as "unmaintained" WBC count is greater than 3 x 109/L and platelet count greater than 50 x 109/L

Dose modifications

  • Cytarabine (Ara-C) reduced to 1000 mg/m2 for patients greater than or equal to 60 years old, creatinine greater than or equal to 1.5 mg/dL or 0 hour MTX level greater than or equal to 20,000 nmol/L
  • Methotrexate (MTX) reduced by 50% for creatinine clearance 10 to 50 mL/min (eliminated for less than 10 mL/min), by 25% to 75% for delayed excretion and/or nephrotoxicity with prior course (dependent on severity) or by 50% for pleural effusions/ascites with drainage of fluid as feasible.

References

  1. Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. link to original article contains verified protocol PubMed

Consolidation/Intensification therapy

BASIC

back to top

BASIC: Brief, Anthracycline-Sparing, Intensive Cyclophosphamide

Regimen

Study Evidence
Kasamon et al. 2012 (J0409) Non-randomized

Preceding treatment

Chemotherapy, part 1

Supportive medications

  • Mesna (Mesnex) 40 mg/kg/day IV in divided doses on days 2 to 5
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 11 and continuing until post-nadir ANC greater than 1000/uL

One course, followed once post-nadir ANC greater than 1000/uL by:

Chemotherapy, part 2

CNS treatment

  • (only given if there was prior CNS involvement):
  • Cytarabine (Ara-C) 100 mg IT once per week for 4 doses, then once every other week for 4 doses
  • Hydrocortisone (Cortef) 50 mg IT is optional (no parameters given)

References

  1. J0409: Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. link to original article contains verified protocol link to PMC article PubMed

CYM

back to top

CYM: CYtarabine, Methotrexate

Regimen

Study Evidence
Diviné et al. 2005 (LMB95) Phase II

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement).

Preceding treatment

Chemotherapy

  • Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 500 mg/m2)
  • Methotrexate (MTX) 3000 mg/m2 IV over 3 hours once on day 1

Supportive medications

CNS prophylaxis

2 cycles; intervals were as short as possible, as soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 109/L

Subsequent treatment

References

  1. LMB95: Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

CYVE

back to top

CYVE: CYtarabine, VEpesid (Etoposide)

Regimen

Study Evidence
Diviné et al. 2005 (LMB95) Phase II, <20 pts in this subgroup

This regimen is for group C (CNS and/or bone marrow involvement). Note the unusual schedule of cytarabine; presumably the low-dose and high-dose portions are given at separate times in the 24 hour period but this detail is not further specified in the manuscript.

Preceding treatment

Chemotherapy

  • Cytarabine (Ara-C) as follows:
    • 50 mg/m2 IV over 12 hours once per day on days 1 to 5
    • 3000 mg/m2 IV over 3 hours once per day on days 2 to 5
  • Etoposide (Vepesid) 200 mg/m2 IV once per day on days 2 to 5

2 cycles; intervals were as short as possible, as soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 109/L

Subsequent treatment

References

  1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

Maintenance therapy

COPAD/CYVE

back to top

COPAD/CYVE: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin) alternating with CYtarabine, VEpesid (Etoposide)

Regimen

Study Evidence
Diviné et al. 2005 (LMB95) Phase II, <20 pts in this subgroup

This regimen is for group C (CNS and/or bone marrow involvement). Note that the days of administration for the CYVE cycles are counted from the start of the respective COPAD cycles.

Preceding treatment

Chemotherapy, COPAD cycles

CNS treatment

Note: this is only given with the first cycle of maintenance; patients with positive CNS at diagnosis were to also undergo 24 Gy of cranial irradiation.

Chemotherapy, CYVE cycles

4 alternating cycles (COPAD, then CYVE, then COPAD, then CYVE)

References

  1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

COPADM

back to top

COPADM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study Evidence
Diviné et al. 2005 (LMB95) Phase II

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement).

Preceding treatment

Chemotherapy

Supportive medications

CNS prophylaxis

One cycle

References

  1. LMB95: Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed