Chemotherapy and Rituximab With or Without Total-Body Irradiation and Peripheral Stem Cell Transplant in Treating Patients With Lymphoma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy, total-body irradiation, and peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving chemotherapy with rituximab followed by combination chemotherapy with or without rituximab, total-body irradiation, and peripheral stem cell transplant works in treating patients with lymphoma.
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma|
- Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]Kaplan-Meier estimates will be used to verify the progression free survival.
|Study Start Date:||November 2006|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Experimental: Induction R-CHOPac Therapy for patients with B-Cell Lymphoma
Patients received 4 cycles if accelerated R-CHOP (cyclophosphamide. doxorubicin, vincristine and prednisone + rituximab) followed by 3 cycles ICE (ifosfamide, carboplatin and etoposide) consolidation therapy.
|Biological: filgrastim Biological: rituximab Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: prednisone Drug: vincristine sulfate Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy|
OUTLINE: Patients are stratified according to risk (low-intermediate vs high-intermediate or high).
Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV over 15 minutes, and vincristine IV over 1-2 minutes on day 1; oral prednisone once daily on days 1-5; and filgrastim (G-CSF) subcutaneously (SC) once daily on days 7-11 or PEG-filgrastim once at least 24 hours after infusion. Patients also receive rituximab IV 2-3 days apart for a total of 2 doses during the week prior to the first course of chemotherapy and on day 1 of courses 2-4 of chemotherapy. Treatment repeats every 14 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
After the completion of induction chemotherapy, patients undergo CT scan and positron emission tomography (PET) scanning. If the PET scan is positive in one or more nodal sites, a repeat biopsy is performed. Patients with a negative PET scan OR a negative repeat biopsy (including no evidence of lymphoma on repeat bone marrow biopsy) are assigned to receive regimen A for consolidation therapy. Patients with a positive repeat biopsy are assigned to receive regimen B for consolidation therapy.
- Regimen A: Patients receive consolidation chemotherapy comprising etoposide IV over 1 hour on days 1-3, ifosfamide IV continuously over 24 hours on day 2, carboplatin IV on day 2, and G-CSF SC once daily on days 5-12 or PEG-filgrastim once at least 24 hours after infusion. Treatment repeats every 14 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity.
- Regimen B: Patients receive consolidation chemotherapy as in regimen A for 3 courses. Patients also receive rituximab IV on days -3 to -1 of course 3 of chemotherapy. Patients undergo leukapheresis at the completion of course 3 (G-CSF continues from day 5 until the end of leukapheresis). After completion of leukapheresis, patients begin a regimen of high-dose chemoradiotherapy comprising either total body irradiation twice daily on days -10 to -7 and ifosfamide IV over 1 hour and etoposide IV continuously on days -6 to -2 or BEAM chemotherapy comprising carmustine, etoposide, cytarabine, and melphalan. Autologous peripheral blood stem cells (APBSC) are reinfused on day 0. Patients also receive G-CSF SC daily beginning on day 5 and continuing until blood counts recover. Beginning on day 42 post-APBSC, if blood counts have recovered, patients receive rituximab IV once weekly for 4 weeks. Rituximab is repeated beginning on day 180 in the absence of disease progression.
Patients who receive consolidation therapy on regimen A are followed at 4-6 weeks after chemotherapy and patients who receive consolidation therapy on regimen B are followed at 90-120 days after transplantation. All patients are followed closely for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 40-98 patients will be accrued for this study within 4 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00039195
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Study Chair:||Craig Moskowitz, MD||Memorial Sloan Kettering Cancer Center|