Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: 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. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving rituximab and cyclophosphamide together with pegfilgrastim may be effective in treating leukemia or non-Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving rituximab and cyclophosphamide together with pegfilgrastim works in treating patients with B-cell leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.

Detailed Description
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OBJECTIVES: Determine the safety of high-dose cyclophosphamide, rituximab, and pegfilgrastim in patients with B-cell leukemia or low-grade or mantle cell lymphoma. Determine the molecular response rate in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive rituximab IV over 30-60 minutes on days 1, 4, 8,11, 45, and 52, cyclophosphamide IV over 1 hour on days 15-18, and pegfilgrastim subcutaneously on day 19 or 20 in the absence of unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study.

Official Title
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Phase II Study of High Dose Cyclophosphamide and Rituximab in Low Grade and Mantle Cell Lymphoma

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: Pegfilgrastim
* Biological: Rituximab
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following B-cell leukemias or lymphomas, as defined by World Health Organization criteria: Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic leukemia Marginal zone lymphoma (splenic, extranodal, or nodal) Follicular lymphoma (grade 1 or 2) Mantle cell lymphoma No more than minimal (approximately 10%) morphologically identifiable cancer cells on bone marrow biopsy When cancer cells are morphologically difficult to distinguish from normal cells, flow cytometry must show no more than 10% identifiable cancer cells Must have received ≤ 12 months of prior cytotoxic therapy, achieving at least a partial response NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,000/mm^3 Hemoglobin ≥ 10.0 g/dL Platelet count ≥ 75,000/mm^3 Serum creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 2 mg/dL unless secondary to tumor AST or ALT < 2 times upper limit of normal Normal (≥ 45%) left ventricular cardiac ejection fraction (determined by echocardiogram or MUGA scan) DLCO > 50% predicted Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known sensitivity to E. coli-derived products (e.g. filgrastim [G-CSF], insulin, asparaginase, growth hormone, or recombinant interferon alfa-2b) or any treatment study drugs No active infections requiring oral or intravenous antibiotics No other second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix unless the malignancy was localized and treated or resected with > 90% probability of cure PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior anti-CD20 therapy allowed provided patient achieved a partial or complete response No concurrent steroids during rituximab administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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-HiCy<br>Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support. | Biological: Pegfilgrastim<br>* 6 mg SQ 24-48 hours after last dose of cyclophosphamide.<br>* Other names: Neulasta;Biological: Rituximab<br>* 375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* 50 mg/kg/day on Days 15, 16, 17, and 18.<br>* Other names: CTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment | Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count >= 500 cells per microliter; platelet recovery is defined as untransfused platelet count >= 20 * 10^9 cells per liter. | Up to 43 days | 
| Non-relapse Mortality | Number of participants who died for reasons related to protocol treatment. | 5 years | 
| Event-free Survival | Percentage of participants alive without disease relapse. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, Waldenstrom macroglobulinemia, prolymphocytic leukemia, stage I marginal zone lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III marginal zone lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, stage IV marginal zone lymphoma