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

Alliance for Clinical Trials in Oncology105 enrolled

Overview

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.

Interventions

filgrastimBIOLOGICAL

5 ug/kg/day sub Q injection day 7 until ANC\>5000/ul courses II-VII

rituximabBIOLOGICAL

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

cyclophosphamideDRUG

200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII

cytarabineDRUG

1 g/sq m/day IV infusion Days 4 \& 5, courses II, IV, VI

dexamethasoneDRUG

10mg/sq m PO or IV Days 1-5 courses II-VII

doxorubicin hydrochlorideDRUG

25 mg/sq m/day IV infusion Days 4 \& 5 courses III,V, VII

etoposideDRUG

80 mg/sq m/day IV infusion Days 4 \& 5 courses II, IV, VI

ifosfamideDRUG

800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI

leucovorin calciumDRUG

25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX \<10nM, courses II-VII

methotrexateDRUG

1.5 g/sq m IV infusion Day 1 courses II-VII

prednisoneDRUG

60 mg/sq m PO/day Days 1-7 course I

vincristine sulfateDRUG

2 mg IV push Day 1 courses II-VII

AllopurinolDRUG

300 mg/day PO Days 1-14, course I

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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

Locations (31)

Naval Medical Center - San Diego

San Diego, California, United States

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

University of Illinois Cancer Center

Chicago, Illinois, United States

Outcomes

Primary Outcomes

Complete Response Rate

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

Time frame: 6 months

Secondary Outcomes

2 Year Event Free Survival

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.

Time frame: 2 years

2 Year Overall Survival

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