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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: dexamethasone
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: ifosfamide
* Drug: leucovorin calcium
* Drug: methotrexate
* Drug: prednisone
* Drug: vincristine sulfate
* Drug: Allopurinol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab with High Intensity Chemotherapy<br>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) | Biological: filgrastim<br>* 5 ug/kg/day sub Q injection day 7 until ANC>5000/ul courses II-VII<br>Biological: rituximab<br>* 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<br>Drug: cyclophosphamide<br>* 200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII<br>Drug: cytarabine<br>* 1 g/sq m/day IV infusion Days 4 & 5, courses II, IV, VI<br>Drug: dexamethasone<br>* 10mg/sq m PO or IV Days 1-5 courses II-VII<br>Drug: doxorubicin hydrochloride<br>* 25 mg/sq m/day IV infusion Days 4 & 5 courses III,V, VII<br>Drug: etoposide<br>* 80 mg/sq m/day IV infusion Days 4 & 5 courses II, IV, VI<br>Drug: ifosfamide<br>* 800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI<br>Drug: leucovorin calcium<br>* 25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX <10nM, courses II-VII<br>Drug: methotrexate<br>* 1.5 g/sq m IV infusion Day 1 courses II-VII<br>Drug: prednisone<br>* 60 mg/sq m PO/day Days 1-7 course I<br>Drug: vincristine sulfate<br>* 2 mg IV push Day 1 courses II-VII<br>Drug: Allopurinol<br>* 300 mg/day PO Days 1-14, course I<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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