Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed or Progressive B-Cell Diffuse Large Cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether stem cell transplantation is more effective with or without rituximab in treating relapsed or progressive B-cell diffuse large cell lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of stem cell transplantation with or without rituximab in treating patients who have relapsed or progressive B-cell diffuse large cell lymphoma.

Detailed Description
-----------------
OBJECTIVES: Compare disease-free survival of patients with relapsed or progressive B-cell diffuse large cell lymphoma undergoing stem cell transplantation with or without post-transplant rituximab. Evaluate the effect of rituximab, administered post-transplant, on the procedure-related mortality of these patients. Determine the potential infectious complications of the addition of this drug to autologous stem cell transplantation in these patients. Compare overall survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to relapse (relapsed more than 6 months after either initial complete remission [CR] or CR with positive positron emission tomography or MRI [gallium] vs failed to achieve initial CR or relapsed within 6 months after either initial CR or CR with positive PET or MRI [gallium]) and prior rituximab (yes vs no). Stem cell mobilization Patients receive rituximab IV over 4-8 hours on days 1 and 5. Patients also receive cyclophosphamide IV over 2 hours on day 8 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until the last day of apheresis. Stem cells are collected over 1-3 days. Preparative regimen Regimen A (patients who have received prior radiotherapy or are ≥ 61 years of age): Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Regimen B (all other patients): Patients undergo total body irradiation twice daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Stem cells are reinfused on day 0. Patients are then randomized to one of two post-transplant treatment arms. Post-transplant treatment Arm I (rituximab): Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Patients receive rituximab IV over 4-8 hours every 7 days for 4 doses, starting on day 45 post-transplant. Course of rituximab is repeated beginning on day 180 post-transplant. Arm II (no rituximab): Patients receive G-CSF as in arm I. Patients are followed for 10 years. PROJECTED ACCRUAL: A total of 427 patients will be accrued for this study within 3.5 years.

Official Title
-----------------
Randomized Phase III Trial Of Rituximab (NSC #687451) And Autologous Stem Cell Transplantation For B Cell Diffuse Large Cell Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Biological: filgrastim
* Biological: rituximab
* Drug: carmustine
* Drug: cyclophosphamide
* Drug: etoposide
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of diffuse large cell lymphoma and meeting the following criteria: B-cell type with expression of CD20 either at diagnosis or at relapse Relapse after having achieved an initial complete remission (CR) or failure to achieve initial CR (residual radiographic abnormalities after primary therapy allowed if these abnormalities are also positive by positron emission tomography or MRI [gallium]) No newly diagnosed disease No progressive or stable disease to most recent salvage therapy PATIENT CHARACTERISTICS: Age 18 to 70 Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 2.0 mg/dL AST or ALT < 3 times upper limit of normal Renal Creatinine ≤ 2.0 mg/dL OR Creatinine clearance ≥ 40 mL/min Cardiovascular Cardiac ejection fraction ≥ 40% Pulmonary DLCO ≥ 60% of predicted Other No other malignancy within the past 2 years except basal cell skin cancer or carcinoma in situ of the cervix No active infection requiring oral or IV antibiotics HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Chemotherapy No more than 3 prior immunotherapy regimens Chemotherapy No more than 3 prior chemotherapy regimens Addition of radiation or a monoclonal antibody to chemotherapy is considered one treatment regimen if the addition was part of the initial treatment plan Addition of these therapies due to lack of response or poor response would be considered an additional treatment regimen whether given in front-line or salvage setting Endocrine therapy Not specified Radiotherapy See Chemotherapy No more than 3 prior radiotherapy regimens No prior radioimmunotherapy Surgery Not specified

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Biological: rituximab|nan|
|Drug: carmustine|nan|
|Drug: cyclophosphamide|nan|
|Drug: etoposide|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure-related mortality |  |  | 
| Overall survival |  |  | 
| Potential infectious complications of the addition of rituximab to autologous stem cell transplantation |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent adult diffuse large cell lymphoma