Cyclophosphamide W/or W/Out Rituximab and Peripheral Stem Cell Transplantation in Patients With Recurrent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-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. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known if combining rituximab with cyclophosphamide is more effective than cyclophosphamide alone in stimulating peripheral stem cells for transplantation. PURPOSE: This randomized phase II trial is studying how well giving cyclophosphamide with or without rituximab followed by chemotherapy and peripheral stem cell transplantation works in treating patients with recurrent non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Compare the effects of mobilization therapy with or without rituximab on hematopoietic stem cells, B and T lymphocytes, and natural killer cells in patients with advanced or recurrent B-cell non-Hodgkin's lymphoma. Compare the effects of B-lymphocyte purging using concurrent rituximab and mobilization therapy vs a CD34+ cell enrichment device on hematopoietic stem cells, B and T lymphocytes, and natural killer cells in the peripheral blood stem cell (PBSC) infusates. Compare the effect of these purging regimens on tumor cell content of PBSC infusates. Compare the effects of these regimens on myeloid and lymphoid engraftment after high-dose chemotherapy and autologous PBSC infusion in these patients. Compare post-transplantation infection complications in patients treated with these regimens. Compare the response and relapse-free survival of patients treated with these regimens. OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive mobilization therapy comprising rituximab IV over 2-5 hours on days 1, 8, and 15 and cyclophosphamide IV over 3-6 hours on day 16. Beginning 36-48 hours after the completion of cyclophosphamide, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Patients then undergo peripheral blood stem cell (PBSC) collection. After completion of PBSC collection, patients receive high-dose chemotherapy comprising carmustine IV on days -7 to -3 and etoposide IV and cisplatin IV for 3 days during days -7 to -3. Patients may undergo involved-field radiotherapy to active or previously bulky (more than 5 cm) tumors daily for 7-10 days. Patients receive unmanipulated PBSCs on day 0. Patients receive G-CSF SC daily beginning 4 hours after completion of PBSC infusion and continuing until neutrophil engraftment. Arm II: Patients receive mobilization therapy comprising cyclophosphamide and G-CSF and high-dose chemotherapy comprising carmustine, etoposide, and cisplatin as in arm I. Patients may also undergo involved-field radiotherapy as in arm I. Patients receive CD34 cell-enriched PBSC on day 0 followed by G-CSF as in arm I. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2 years.

Official Title
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Randomized Phase II Trial of B-Lymphocyte Purging of Autologous Peripheral Blood Progenitor Cells in Patients With B-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: rituximab
* Drug: carmustine
* Drug: cisplatin
* Drug: cyclophosphamide
* Drug: etoposide
* Procedure: bone marrow ablation with stem cell support
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL) Indolent or aggressive histology No small lymphocytic lymphoma, Burkitt's lymphoma, or small lymphocytic non-Burkitt's lymphoma CD20-positive and/or CD19-positive by immunohistochemistry or flow cytometry Second or greater remission allowed Partial remission, relapse, or refractory disease must have measurable tumor Eligible for high-dose therapy followed by autologous peripheral blood stem cell transplantation No CNS involvement by lymphoma PATIENT CHARACTERISTICS: Age: 12 to 65 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,200/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin less than 2.0 mg/dL Renal: Creatinine clearance at least 60 mL/min No renal dysfunction Cardiovascular: LVEF at least 40% No cardiac dysfunction No myocardial infarction within the past 3 months Pulmonary: FEV_1 greater than 60% DLCO at least 60% of predicted No pulmonary dysfunction No asthma Other: HIV negative No significant organ dysfunction No severe comorbid condition No uncontrolled diabetes No severe or active infection Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Chemotherapy No prior immunotherapy Chemotherapy: No prior high-dose chemotherapy with or without peripheral blood stem cell transplantation No more than 3 prior chemotherapy regimens for NHL At least 4 weeks since prior chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: with rituximab IV<br> | Biological: filgrastim<br>* Beginning 36-48 hours after the completion of cyclophosphamide, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Patients receive G-CSF SC daily beginning 4 hours after completion of PBSC infusion and continuing until neutrophil engraftment.<br>Biological: rituximab<br>* rituximab IV over 2-5 hours on days 1, 8, and 15<br>Drug: carmustine<br>* After completion of PBSC collection, patients receive high-dose chemotherapy comprising carmustine IV on days -7 to -3<br>Drug: cisplatin<br>* After completion of PBSC collection, cisplatin IV for 3 days during days -7 to -3.<br>Drug: cyclophosphamide<br>* cyclophosphamide IV over 3-6 hours on day 16.<br>Drug: etoposide<br>* After completion of PBSC collection, etoposide IV for 3 days during days -7 to -3.<br>Procedure: bone marrow ablation with stem cell support<br>* Patients then undergo peripheral blood stem cell (PBSC) collection.<br>Procedure: peripheral blood stem cell transplantation<br>* Arm I: Patients receive unmanipulated PBSCs on day 0. Arm II: Patients receive CD34 cell-enriched PBSC on day 0.<br>Radiation: radiation therapy<br>* Patients may undergo involved-field radiotherapy to active or previously bulky (more than 5 cm) tumors daily for 7-10 days.<br>|
| Active Comparator: Arm II: without rituximab IV<br> | Biological: filgrastim<br>* Beginning 36-48 hours after the completion of cyclophosphamide, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Patients receive G-CSF SC daily beginning 4 hours after completion of PBSC infusion and continuing until neutrophil engraftment.<br>Drug: carmustine<br>* After completion of PBSC collection, patients receive high-dose chemotherapy comprising carmustine IV on days -7 to -3<br>Drug: cisplatin<br>* After completion of PBSC collection, cisplatin IV for 3 days during days -7 to -3.<br>Drug: cyclophosphamide<br>* cyclophosphamide IV over 3-6 hours on day 16.<br>Drug: etoposide<br>* After completion of PBSC collection, etoposide IV for 3 days during days -7 to -3.<br>Procedure: bone marrow ablation with stem cell support<br>* Patients then undergo peripheral blood stem cell (PBSC) collection.<br>Procedure: peripheral blood stem cell transplantation<br>* Arm I: Patients receive unmanipulated PBSCs on day 0. Arm II: Patients receive CD34 cell-enriched PBSC on day 0.<br>Radiation: radiation therapy<br>* Patients may undergo involved-field radiotherapy to active or previously bulky (more than 5 cm) tumors daily for 7-10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total CD34 cells |  | measured at baseline, at time of harvests, days 42 and 90 after the transplant, and 6 and 12 months after the transplant | 
| T and B lymphocyte counts |  | measured at baseline, at time of harvests, days 42 and 90 after the transplant, and 6 and 12 months after the transplant | 
| Disease response |  | measured at 4 weeks after the transplant | 
| Engraftment |  | measured at days 42 and 90 after the transplant, and 6 and 12 months after the transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma