Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia

Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia

Phase II Study Of Rituximab And Short Duration, High Intensity Chemotherapy With G-CSF Support In Previously Untreated Patients With Burkitt Lymphoma/Leukemia

RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the numbers of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with rituximab and filgrastim may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab with chemotherapy and filgrastim in treating patients who have Burkitt's lymphoma or Burkitt's leukemia.

OBJECTIVES: Determine the complete response rate in patients with previously untreated Burkitt's lymphoma or Burkitt's leukemia treated with rituximab and high-intensity chemotherapy with filgrastim (G-CSF) support. Determine the progression-free and overall survival of patients treated with this regimen. Determine the feasibility and toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to disease (leukemia vs lymphoma). Course 1: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5 and oral prednisone on days 1-7. Allopurinol PO will be given on days 1-14. Courses 2, 4, and 6: Patients receive ifosfamide IV over 1 hour daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV over 15 minutes every 6 hours on day 2; cytarabine IV over 2 hours on days 4 and 5 and etoposide IV over 1 hour daily on days 4 and 5; oral dexamethasone daily on days 1-5; and methotrexate and cytarabine intrathecally (IT) on day 1. During course 2, patients receive rituximab IV over 1-4 hours on days 8, 10, and 12. During courses 4 and 6, patients receive rituximab IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 7 and continuing until blood counts recover. Courses 3, 5, and 7: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV every 6 hours on day 2; doxorubicin IV daily on days 4 and 5; oral dexamethasone daily on days 1-5; methotrexate and cytarabine IT on day 1; and rituximab IV over 1 hour on day 8. Patients also receive G-CSF as in courses 2, 4, and 6. After course 3, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 100 patients (50 per stratum) will be accrued for this study within 3 years.

untreated adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma

Cycle1: Cyclophosphamide 100 mg/m^2/day (d) IV (d 1-5), Prednisone 60 mg/m^2/d oral (d 1-7), Allopurinal 300 mg/d oral (d 1-14) Cycle 2, 4 & 6 (21 day): Ifosfamide 800 mg/m^2/d (d 1-5), Dexamethasone 10 mg/m^2/d (d1-5), Methotrexate 150 mg/m^2 load, then 1.35 g/m^2 over 23.5 h (d 1), Leucovorin 25 mg/m^2 36 h after methotrexate (d 2) then 10 mg/m^2 every 6 h, Vincristine 2 mg push (d 1), Cytarabine 1000 mg/m^2/d over 2 h (d 4-5), Etoposide 80 mg/m^2.d over 1 h (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 50 mg/m^2 d 8 cycle 2 only, 375 mg/m^2/d (d 10, 12 cycle 2, d 8 cycle 4 & 6) Cycle 3, 5 & 7 (21 day): Cyclophosphamide 200 mg/m^2/day (d) IV (d 1-5), Dexamethasone 10 mg/m^2/d (d1-5), Methotrexate 150 mg/m^2 load, then 1.35 g/m^2 over 23.5 h (d 1), Leucovorin 50 mg/m^2 36 h after methotrexate (d 2) then 10 mg/m^2 every 6 h, Vincristine 2 mg push (d 1), Doxorubicin 25 mg/m^2/d (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 375 mg/m^2/d (d 8)

Day 8 course II 50 mg/sq m IV infusion: d 8 course IV & VI 375mg/sq m IV Day 10 course II: 325 mg/sq m IV infusion Day 12 course II: 375 mg/sq m IV infusion

Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease.

Percentage of patients who were event free at 2 years. The 2-year event free rate was estimated using the Kaplan Meier method. An event is defined as death, progression or treatment failure.

Percentage of participants who were alive at 2 years. The 2 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

DISEASE CHARACTERISTICS: Histologically, cytogenetically, or immunophenotypically confirmed Burkitt's leukemia or Burkitt's or Burkitt-like lymphoma L3 morphology surface IgG expression Cytogenetic evidence for t(8;14), t(8;22), or t(2;8) Previously untreated disease except hydroxyurea for leukocytosis CNS involvement allowed Patients with Burkitt's leukemia or Burkitt's lymphoma with bone marrow involvement must also be enrolled on CALGB-8461 Patients with Burkitt's leukemia must also be enrolled on CALGB-9665 PATIENT CHARACTERISTICS: Age: 16 and over Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) Renal: Creatinine no greater than 1.5 times ULN Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent interleukin-11 Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes) No concurrent steroids except for adrenal failure Radiotherapy: No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

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. doi: 10.1111/bjh.12736. Epub 2014 Jan 15.