Non-Hodgkin Lymphoma (NHL) Treatment Regimens: Burkitt Lymphoma

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NON-HODGKIN LYMPHOMA TREATMENT REGIMENS:

Burkitt Lymphoma

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The non-hodgkin lymphoma (burkitt lymphoma) cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These non-hodgkin lymphoma (burkitt lymphoma) cancer treatment regimens regimens are provided only to supplement the latest treatment strategies.

These Cancer Treatment Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

(Revised 2/2017)

© 2017 by Haymarket Media, Inc.

Induction Therapy—Low Risk1a

Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

CALGB 100022

Cycle 1:

Day 1: Triple intrathecal therapy for CNS prophylaxis

Days 1–5: Cyclophosphamide 200mg/m2 IV

Days 1–7: Prednisone 60mg/m2 orally.

Cycles 2 (beginning Day 8), 4, and 6:

Day 1: Triple intrathecal therapy for CNS prophylaxis

Days 1–5: Ifosfamide 800mg/m2 IV + dexamethasone 10mg/m2 IV

Day 1: Methotrexate 1.5g/m2 IV (with leucovorin rescue) + vincristine 2mg IV

Days 4 and 5: Cytarabine 1g/m2 IV + etoposide 80mg/m2 IV

Day 8: Rituximab 50mg/m2 IV for cycle 2, then 375mg/m2 IV for cycles 4 and 6

Days 10 and 12 (Cycle 2 only): Rituximab 375mg/m2 IV.

Cycles 3, 5, and 7:

Day 1: Triple intrathecal therapy for CNS prophylaxis

Days 1–5: Cyclophosphamide 200mg/m2 IV + dexamethasone 10mg/m2 IV

Day 1: Methotrexate 1.5g/m2 IV + vincristine 2mg IV

Days 4 and 5: Doxorubicin 25mg/m2 IV

Day 8: Rituximab 375mg/m2 IV.

Deliver cycles every 21 days.

CODOX-M (original or modified)

(cyclophosphamide + doxorubicin + vincristine with intrathecal MTX + cytarabine, followed by systemic MTX and cytarabine) ± Rituximab3

Day 1: Cyclophosphamide 800mg/m2 IV + doxorubicin 40mg/m2 IV

Days 2–5: Cyclophosphamide 200mg/m2/day IV

Days 1 and 3: Cytarabine 70mg intrathecally

Days 1 and 8: Vincristine 1.5mg/m2 IV

Day 10: Methotrexate 1,200mg/m2 IV over 1 hour, then 240mg/m2/hour continuous IV infusion for the next 23 hours

Day 11: Leucovorin 192mg/m2 IV 36 hours after initiation of MTX, followed by leucovorin 12mg/m2 IV every 6 hours until MTX level <5 x 10–8 M

Day 13: G-CSF 5µg/kg SC daily beginning 24 hours after initiation of leucovorin until absolute granulocyte count ≥1 x 109/L

Day 15: Methotrexate 12mg intrathecally

Day 16: Leucovorin 15mg orally given 24 hours after intrathecal MTX, ±

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 21 days for 3 cycles.

Dose-adjusted EPOCH (etoposide + prednisone + vincristine + cyclophosphamide + doxorubicin) + intrathecal MTX + rituximab4–6b

Day 1: Rituximab 375mg/m2 IV

Days 1–4: Etoposide 50mg/m2 continuous IV infusion + doxorubicin 10mg/m2 continuous IV infusion + vincristine 0.4mg/m2 continuous IV infusion

Days 1–5: Prednisone 60mg/m2 orally twice daily.

Day 5: Cyclophosphamide 750mg/m2 IV

Day 6: G-CSF 300µg administered until ANC >5,000cells/µL

Days 1 and 5 (Cycles 3–6): Methotrexate 12mg intrathecally.

Repeat cycle every 3 weeks for 6 cycles.

HyperCVAD (cyclophosphamide

+ vincristine + doxorubicin + dexamethasone alternating with high-dose methotrexate and cytarabine)7,8

Cycles 1, 3, 5, and 7—HyperCVAD

Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours for 6 doses + mesna 600mg/m2 continuous IV infusion

Days 4 and 11: Vincristine 2mg IV

Day 4: Doxorubicin 50mg/m2 IV

Days 1–4 and Days 11–14: Dexamethasone 40mg IV daily

Days 1 and 11 (Cycles 1 and 3 only): Rituximab 375mg/m2 IV.

Cycles 2, 4, 6, 8—High-dose MTX and Cytarabine

Day 1: MTX 1g/m2 IV over 24 hours

Days 2 and 3: Cytarabine 3g/m2 IV every 12 hours for 4 doses

Days 2 and 8 (Cycles 2 and 4): Rituximab 375mg/m2 IV.

Repeat every 3 weeks for 8 cycles.

Combination Regimens—High-Risk1a

CALGB 100022

Cycle 1:

Day 1: Triple intrathecal therapy for CNS prophylaxis

Days 1–5: Cyclophosphamide 200mg/m2 IV

Days 1–7: Prednisone 60mg/m2 orally.

Cycles 2 (beginning Day 8), 4, and 6:

Day 1: Triple intrathecal therapy for CNS prophylaxis

Days 1–5: Ifosfamide 800mg/m2 IV + dexamethasone 10mg/m2 IV

Day 1: Methotrexate 1.5g/m2 IV (with leucovorin rescue) + vincristine 2mg IV

Days 4 and 5: Cytarabine 1g/m2 IV + etoposide 80mg/m2 IV

Day 8: Rituximab 50mg/m2 IV for cycle 2, then 375mg/m2 IV for cycles 4 and 6

Days 10 and 12 (Cycle 2 only): Rituximab 375mg/m2 IV.

Cycles 3, 5, and 7:

Day 1: Triple intrathecal therapy for CNS prophylaxis

Days 1–5: Cyclophosphamide 200mg/m2 IV + dexamethasone 10mg/m2 IV

Day 1: Methotrexate 1.5g/m2 IV + vincristine 2mg IV

Days 4 and 5: Doxorubicin 25mg/m2 IV

Day 8: Rituximab 375mg/m2 IV.

Deliver cycles every 21 days.

CODOX-M (original or modified) (cyclophosphamide + doxorubicin + vincristine, plus intrathecal MTX + cytarabine, followed by systemic MTX) alternating with IVAC (ifosfamide + cytarabine + etoposide) and intrathecal MTX

± Rituximab3,9,10

Day 1: Cyclophosphamide 800mg/m2 IV + doxorubicin 40mg/m2 IV

Days 2–5: Cyclophosphamide 200mg/m2/day IV

Days 1 and 3: Cytarabine 70mg intrathecally

Days 1 and 8: Vincristine 1.5mg/m2 IV

Day 10: Methotrexate 1,200mg/m2 IV over 1 hour, then 240mg/m2/hour continuous IV infusion for the next 23 hours

Day 11: Leucovorin 192mg/m2 IV 36 hours after initiation of MTX, followed by leucovorin 12mg/m2 IV every 6 hours until MTX level <5 x 10–8 M

Day 13: G-CSF 5µg/kg SC daily beginning 24 hours after initiation of leucovorin until absolute granulocyte count ≥1 x 109/L

Day 15: Methotrexate 12mg intrathecally

Day 16: Leucovorin 15mg orally given 24 hours after intrathecal MTX, ±

Day 1: Rituximab 375mg/m2 IV.

Alternate Cycles With:

Day 1: Cytarabine 2g/m2 IV every 12 hours for 4 doses.

Days 1–5: Etoposide 60mg/m2 IV + ifosfamide 1,500mg/m2 IV, plus mesna 360mg/m2

Day 5: Methotrexate 12mg intrathecally

Day 6: Leucovorin 15mg orally 24 hours after intrathecal MTX

Day 7: G-CSF 5µg/kg SC daily until absolute granulocyte count ≥1 x 109/L, ±

Day 1: Rituximab 375 mg/m2 IV.

Repeat for 4 cycles alternating between CODOX-M and IVAC regimens.

Dose-adjusted EPOCH (etoposide + prednisone + vincristine + cyclophosphamide

+ doxorubicin) + intrathecal MTX + Rituximab4–6b

Day 1: Rituximab 375mg/m2 IV

Days 1–4: Etoposide 50mg/m2 continuous IV infusion + doxorubicin 10mg/m2 continuous IV infusion + vincristine 0.4mg/m2 continuous IV infusion

Days 1–5: Prednisone 60mg/m2 orally twice daily

Day 5: Cyclophosphamide 750mg/m2 IV

Day 6: G-CSF 300µg administered until ANC >5,000cells/µL

Days 1 and 5 (Cycles 3–6): Methotrexate 12mg intrathecally.

Repeat cycle every 3 weeks for 6 cycles.

HyperCVAD (cyclophosphamide

+ vincristine + doxorubicin + dexamethasone alternating with high-dose methotrexate and cytarabine) + Rituximab7,8

Cycles 1, 3, 5, and 7—HyperCVAD

Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours for 6 doses + mesna 600mg/m2 continuous IV infusion

Days 4 and 11: Vincristine 2mg IV

Day 4: Doxorubicin 50mg/m2 IV

Days 1–4 and Days 11–14: Dexamethasone 40mg IV daily

Days 1 and 11 (Cycles 1 and 3 only): Rituximab 375mg/m2 IV

Cycles 2, 4, 6, 8—High-dose MTX and Cytarabine

Day 1: MTX 1g/m2 IV over 24 hours

Days 2 and 3: Cytarabine 3g/m2 IV every 12 hours for 4 doses

Days 2 and 8 (Cycles 2 and 4): Rituximab 375mg/m2 IV.

Repeat every 3 weeks for 8 cycles.

Second Line Therapy1a

Dose-adjusted EPOCH (etoposide + prednisone + vincristine + cyclophosphamide

+ doxorubicin) + intrathecal MTX + Rituximab4–6b

Day 1: Rituximab 375mg/m2 IV

Days 1–4: Etoposide 50mg/m2 continuous IV infusion + doxorubicin 10mg/m2 continuous IV infusion + vincristine 0.4mg/m2 continuous IV infusion

Days 1–5: Prednisone 60mg/m2 orally twice daily

Day 5: Cyclophosphamide 750mg/m2 IV

Day 6: G-CSF 300µg administered until ANC >5,000cells/µL

Days 1 and 5 (Cycles 3–6): Methotrexate 12mg intrathecally.

Repeat cycle every 3 weeks for 6 cycles.

RICE (rituximab + ifosfamide + carboplatin + etoposide)11

Day 1: Rituximab 375mg/m2 IV

Day 2: Ifosfamide 5,000mg/m2 and Mesna 5,000mg/m2 IV + carboplatin AUC 5 mg min/mL (maximum 800mg) IV

Day 1–3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 weeks.

RIVAC (rituximab + ifosfamide + cytarabine + etoposide)10

Day 1: Rituximab 375mg/m2 IV

Day 1: Cytarabine 2g/m2 IV every 12 hours for 4 doses

Days 1–5: Etoposide 60mg/m2 IV + ifosfamide 1,500mg/m2 IV, plus mesna 360mg/m2

Day 5: Methotrexate 12mg intrathecally

Day 6: Leucovorin 15mg orally 24 hours after intrathecal MTX

Day 7: G-CSF 5µg/kg SC daily until absolute granulocyte count ≥1 x 109/L.

Repeat cycle every 3 weeks.

RGDP (rituximab + gemcitabine + dexamethasone + cisplatin)12

Day 1: Rituximab 375mg/m2 IV

Day 1 and 8: Gemcitabine 1,000mg/m2 IV

Day 1–3: Cisplatin 25mg/m2 IV

Day 1–4: Dexamethasone 40mg IV.

Repeat cycle every 3 weeks.

HDAC + Rituximab13

Days 1, 3, and 5: High-dose cytarabine 3g/m2 IV every 12 hours

Day 1: Rituximab 375mg/m2 IV.

Repeat for 4 cycles.

a All regimens for Burkitt lymphoma include CNS prophylaxis/therapy.

b For patients without CNS disease

References

1. NCCN Clinical Practice guidelines in Oncology™. B-cell Lymphomas. v 1.2017. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed January 24, 2017.

2. Rizzieri DA, Johnson JL, Byrd JC, et al. Efficacy and toxicity of rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or Burkitt–like leukemia/ lymphoma: Cancer and Leukemia Group B (Calgb) study 10002. Presented at American Society of Hematology Annual Meeting and Exposition; December 4–7, 2010; Orlando, FL. Blood. 2010;116:Abstract 858.

3. Lacasce A, Howard O, Li S, et al. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004;45:761–767.

4. Dunleavy K, Wayne A, Little R, et al. The addition of rituximab to dose-adjusted EPOCH with HAART suspension is highly effective and tolerable in AIDS-related lymphoma (ARL) and allows the delivery of abbreviated chemotherapy. Poster presented at: American Society of Hematology Annual Meeting and Exposition; December 10–13, 2005; Atlanta, GA. Blood. 2005;106:Abstract 930.

5. Dunleavy K, Little RF, Pittaluga S, et al. A prospective study of dose-adjusted EPOCH with rituximab in adult patients with newly diagnosed Burkitt lymphoma: a regimen with high efficacy and low toxicity. 10th International Conference on Malignant Lymphomas Abstracts. Ann Oncol. 2008;19(suppl 4):iv83–iv84.

6. Wilson WH, Grossbard ML, Pittaluga S, et al. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002;99:2685–2693.

7. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-like lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569–1580.

8. Thomas DA, Kantarjian HM, Cortes J, et al. Long-term outcome after hyper-CVAD and rituximab chemoimmunotherapy for Burkitt (BL) or Burkitt-like (BLL) leukemia/lymphoma and mature B-cell acute lymphocytic leukemia (ALL). Poster presented at: American Society of Hematology Annual Meeting and Exposition; December 6–9, 2008; San Francisco, CA. Blood. 2008;112:Abstract 1929.

9. Mead GM, Sydes MR, Walewski J, et al. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adults Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002;13:1264–1274.

10. Barnes JA, Lacasce AS, Feng Y, et al. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011;22:1859–1864.

11. Griffin TC, Weitzman S, Weinstein H et al. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009;52:177–181.

12. Fan Y, Huang ZY, Luo LH, Yu HF. Efficacy of GDP regimen on relapsed or refractory aggressive non-Hodgkin's lymphoma: a report of 24 cases. Ai Zheng. 2008;27(11):1222–1225.

13. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994;331:896–903.


Hematologic Cancer Drug Monographs

Leukemias, Lymphomas, And Other Hematologic Cancers

ADCETRIS ALKERAN ALKERAN FOR INJECTION
ARRANON ARZERRA BELEODAQ
BENDEKA BEXXAR BICNU
BLEOMYCIN BLINCYTO BOSULIF
BUSULFEX CAMPATH CERUBIDINE
CLADRIBINE CLOLAR CYCLOPHOSPHAMIDE
CYTARABINE CYTOXAN INJECTION DACOGEN
DARZALEX DEPOCYT DOXIL
DOXORUBICIN HCL DOXORUBICIN HCL SOLUTION DTIC-DOME
EMPLICITI ERWINAZE EVOMELA
FARYDAK FLUDARA FOLOTYN
GAZYVA GLEEVEC GLEOSTINE
HYDREA ICLUSIG IDAMYCIN
IDAMYCIN PFS IMBRUVICA INTRON A
INTRON A SOLN ISTODAX JAKAFI
KEYTRUDA KYPROLIS LEUKERAN
MARQIBO MATULANE METHOTREXATE FOR INJECTION
METHOTREXATE INJECTION MITOXANTRONE HCL MUSTARGEN
MYLERAN NINLARO ONCASPAR
ONTAK OPDIVO PAMIDRONATE DISODIUM INJECTION
PENTOSTATIN POMALYST PURINETHOL
PURIXAN REVLIMID RITUXAN
SPRYCEL SYNRIBO TABLOID
TARGRETIN TARGRETIN GEL TASIGNA
THALOMID TREANDA TREXALL
TRISENOX UVADEX VALCHLOR
VELCADE VENCLEXTA VESANOID
VIDAZA VINBLASTINE FOR INJECTION VINBLASTINE INJECTION
VINCASAR PFS VUMON ZEVALIN
ZOLINZA ZOMETA ZYDELIG

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

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