Rituximab, Carmustine; Cytarabine, Etoposide, & Melphalan; Stem Cell Transplantation for 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, such as carmustine, cytarabine, etoposide, and melphalan, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy followed by autologous hematopoietic stem cell transplantation in treating patients who have B-cell non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the levels of soluble CD20 antigen (sCD20) in the blood before and after treatment with rituximab and carmustine, cytarabine, etoposide, and melphalan followed by autologous hematopoietic stem cell transplantation in patients with CD20-positive B-cell non-Hodgkin's lymphoma. Correlate the effect of changes in levels of sCD20 with clinical outcomes in patients treated with this regimen. Determine the response rate in patients treated with this regimen. Determine the event-free survival of patients treated with this regimen. Determine the toxicity profile of this regimen in these patients. OUTLINE: Patients receive rituximab IV over approximately 3-4 hours once weekly for 2 weeks followed 1 week later by hematopoietic stem cell or bone marrow harvest. Patients then receive a third dose of rituximab IV over approximately 3-4 hours on day -7 or -6. Patients also receive high-dose chemotherapy comprising carmustine IV on day -6, cytarabine IV and etoposide IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplantation on day 0. Patients who have less than a complete remission at day 100 post-transplantation receive 4 additional doses of rituximab IV over approximately 3-4 hours once weekly for 4 weeks. Patients are followed at day 100, at 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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A Phase II Trial Of BEAM/Rituximab/Autologous Hematopoietic Stem Cell Transplantation (AHSCT) For Patients With CD20 Positive Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: carmustine
* Drug: cytarabine
* Drug: etoposide
* Drug: melphalan
* Procedure: autologous bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of non-Hodgkin's lymphoma o Any B cell CD20-positive disease Failed prior primary induction therapy Meets 1 of the following criteria: Chemotherapy-refractory disease Received at least 3 prior chemotherapy regimens Mantle cell lymphoma Eligible for transplantation 19 years old and over WHO 0-2 Life expectancy at least 6 months Absolute neutrophil count ≥ 1,000/mm^3* Platelet count > 50,000/mm^3* Hemoglobin > 9.0 g/dL* o NOTE: *Unless due to lymphomatous involvement of the bone marrow Fertile patients must use 2 methods of effective contraception Exclusion Criteria: No history of T-cell lymphoma Not pregnant or nursing No other concurrent serious disease or condition that would preclude study participation

Ages Eligible for Study
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Minimum Age: 19 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 |
| --- | --- |
| Other: Arm 1<br>Participants receive rituximab IV over approximately 3-4 hours once weekly for 2 weeks followed 1 week later by hematopoietic stem cell or bone marrow harvest. Participants then receive a third dose of rituximab IV over approximately 3-4 hours on day -7 or -6. Patients also receive high-dose chemotherapy comprising carmustine IV on day -6, cytarabine IV and etoposide IV twice daily on days -5 to -2, and melphalan IV on day -1. Participants undergo autologous hematopoietic stem cell transplantation on day 0. Participants who have less than a complete remission at day 100 post-transplantation receive 4 additional doses of rituximab IV over approximately 3-4 hours once weekly for 4 weeks. Participants are followed at day 100, at 1 year, and then annually thereafter. | Biological: rituximab<br> <br> * Other names: Rituxan;Drug: carmustine<br> <br> * Other names: Gliadel Wafer, Bicnu;Drug: cytarabine<br> <br> * Other names: cytosine arabinoside;Drug: etoposide<br> <br> * Other names: Etopophos, Toposar;Drug: melphalan<br> <br> * Other names: Evomela;Procedure: autologous bone marrow transplantation<br> <br> Procedure: peripheral blood stem cell transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of the relationship between levels of sCD20 in the blood of patients with non-Hodgkin's lymphoma pre and post rituximab/BEAM/autologous peripheral blood progenitor cell transplantation (PBPCT) as they relate to clinical outcomes. | To evaluate levels of soluble CD20 antigen (sCD20) in the blood of patients with non-Hodgkin's lymphoma pre and post rituximab/BEAM/autologous hematopoietic stem cell transplantation (AHSCT), and to examine the effect of changes in levels of sCD20 with clinical outcomes. | pre and post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma