Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed Burkitt's lymphoma or leukemia.

Detailed Description
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OBJECTIVES: Primary Determine the overall response rate, 1-year event-free survival, and overall survival of adult patients with newly diagnosed Burkitt or atypical Burkitt lymphoma or leukemia treated with dose-intensified induction therapy comprising cyclophosphamide, vincristine, prednisone, and rituximab followed by consolidation therapy comprising rituximab and high-dose cyclophosphamide. Determine the grade 3 or higher non-hematologic toxic effects and overall tolerability of this regimen in these patients. Secondary Determine the 3-year event-free survival and overall survival of patients treated with this regimen. Determine the general patterns of CNS and systemic relapse in patients treated with this regimen. OUTLINE: This is a multicenter study. Dose-intensified CVP induction therapy: Patients receive cyclophosphamide IV and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5 and rituximab IV on days 1 and 8, and high-dose methotrexate IV with leucovorin calcium IV rescue on day 8. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover. Treatment repeats approximately every 14 days for 2 courses. CNS therapy: Patients receive cytarabine intrathecally (IT) with or without hydrocortisone IT on days 1, 4, and 11 of each induction therapy course. Patients with evidence of CNS involvement by lymphoma continue to receive cytarabine IT twice weekly during any induction therapy treatment delay. Patients who demonstrate CSF clearance receive cytarabine IT once weekly for 4 doses and then once every other week for 4 doses during consolidation therapy. Patients with disease progression during induction therapy or persistent CNS involvement by lymphoma are removed from the study. All other patients proceed to consolidation therapy. Consolidation therapy: Patients receive rituximab IV on day -4 and high-dose cyclophosphamide IV on days -3, -2, -1, and 0. Patients receive G-CSF SC once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Patients then receive rituximab IV once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 3 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

Official Title
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Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: Filgrastim
* Biological: Rituximab
* Drug: Cyclophosphamide
* Drug: Cytarabine
* Drug: Methotrexate
* Drug: Prednisone
* Drug: Hydrocortisone
* Drug: Vincristine
* Drug: Leucovorin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of 1 of the following: Classic, sporadic Burkitt's lymphoma Burkitt's leukemia (FAB L3 acute lymphoblastic leukemia) Atypical Burkitt/Burkitt's-like lymphoma or leukemia, defined by the following criteria: Characteristic morphologic features High proliferative index AND Ki-67 ≥ 85% Any stage allowed Newly diagnosed or untreated disease Steroids allowed PATIENT CHARACTERISTICS: Age 30 and over Performance status Not specified Life expectancy Not specified Renal No known irreversible renal dysfunction that would preclude treatment with high-dose cyclophosphamide Cardiovascular No known significant cardiac dysfunction that would preclude treatment with high-dose cyclophosphamide Other Not pregnant or nursing No known HIV positivity No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for lymphoma A maximum of 2 prior doses of intrathecal chemotherapy are allowed Endocrine therapy Not specified Radiotherapy No prior radiation therapy for lymphoma Surgery Prior complete or incomplete surgical resection of lymphoma allowed

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 120 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: R-CVP + HiCy<br>Protocol intervention consists of two fifteen-day cycles of cyclophosphamide (Cy), vincristine (V), prednisone (P), rituximab (R), with filgrastim support. CNS intervention consists of three days of cytarabine and hydrocortisone and one day of methotrexate (with leucovorin support) for each cycle. After those two cycles, rituximab and high-dose cyclophosphamide (HiCy) will be given. | Biological: Filgrastim<br>* 5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy.<br>* Other names: G-CSF;Biological: Rituximab<br>* 375 mg/m^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m^2 on Day -4 of HiCy and weekly for four weeks after HiCy.<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* 1500 mg/m^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy.<br>* Other names: HiCy;Drug: Cytarabine<br>* 100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.<br>* Other names: Ara-C;Drug: Methotrexate<br>* 3 g/m^2 on Day 8 of each cycle of R-CVP.<br>* Other names: MTX;Drug: Prednisone<br>* 100 mg on Days 1-5 of each cycle of R-CVP.<br>* Other names: Deltasone;Drug: Hydrocortisone<br>* 50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.<br>Drug: Vincristine<br>* 1.4 mg/m^2 on Day 1 of each cycle of R-CVP.<br>* Other names: Oncovin;Drug: Leucovorin<br>* 25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.<br>* Other names: Folinic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Number of participants who have a complete or partial remission (2007 International Working Group criteria). | Up to 3 months | 
| Overall Survival | Percentage of participants alive at 1 year and at 3 years. | 1 year and 3 years | 
| Event-free Survival | Percentage of participants alive without relapse at 1 year and 3 years. | 1 year and 3 years | 
| Percentage of Participants Experiencing Grade 3-5 Toxicity | Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria). | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Pattern | Percentage of participants experiencing central nervous system (CNS) and systemic relapse. | Up to 6 months | 

 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, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma