SWOG-9704 Chemoradiotherapy and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and radiation and kill more cancer cells. It is not yet known whether chemoradiotherapy plus peripheral stem cell transplantation is more effective than combination chemotherapy alone in treating non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying chemoradiotherapy and peripheral stem cell transplantation to see how well they work compared to combination chemotherapy in treating patients with stage II, stage III, or stage IV non-Hodgkin's lymphoma.
Drug: CHOP regimen
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||SWOG-9704 A Randomized Phase III Trial Comparing Early High Dose Chemoradiotherapy and an Autologous Stem Cell Transplant to Conventional Dose CHOP Chemotherapy Plus Rituximab for CD20+ B Cell Lymphomas (With Possible Late Autologous Stem Cell Transplant) for Patients With Diffuse Aggressive Non-Hodgkin's Lymphoma in the High-Intermediate and High Risk International Classification Prognostic Groups|
- Survival [ Time Frame: until death ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: until death ] [ Designated as safety issue: No ]
|Study Start Date:||July 1997|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Active Comparator: CHOP/CHOP-R x 3
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Prednisone 100 mg/day PO Days 1-5 Vincristine 1.4 mg/m2 IV Day 1 Rituximab 375 mg/m2 IV Day 1 This regimen is repeated every 21 days for 8 cycles
375 mg/m2 IV every 21 daysDrug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Procedure: bone marrow ablation with stem cell support
Experimental: CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Prednisone 100 mg/day PO Days 1-5 Vincristine 1.4 mg/m2 IV Day 1 Rituximab 375 mg/m2 IV Day 1 This regimen is repeated every 21 days for 6 cycles followed by autologous stem cell transplant.
375 mg/m2 IV every 21 daysDrug: CHOP regimen Drug: carmustine Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy
- Compare the overall survival and progression-free survival of patients with intermediate- or high-grade non-Hodgkin's lymphoma treated with high-dose chemoradiotherapy and autologous peripheral blood stem cell transplantation (APBSCT) vs conventional dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (or CHOP plus rituximab for CD20+ disease) with possible late APBSCT.
- Compare the toxic effects of these regimens in this patient population.
OUTLINE: This is a randomized study. Patients are stratified according to disease risk (intermediate-high vs high).
Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients with CD20-positive disease also receive rituximab IV on day 1 (or day 0 during course 1 only). Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.
Within 35 days of completing the fifth course, patients with partial or complete response are randomized to one of two treatment arms.
- Arm I: Patients receive CHOP (or CHOP plus rituximab [CHOP-R]) as above. Treatment repeats every 3 weeks for 3 additional courses. After completion of chemotherapy, patients are encouraged to undergo harvest of peripheral blood stem cells (PBSC) for possible use at time of relapse. After completion of 8 courses, patients receive no additional therapy until disease progression or biopsy-proven disease.
- Arm II: Patients receive one additional course of CHOP/CHOP-R followed by filgrastim (G-CSF), sargramostim (GM-CSF), or other colony-stimulating factors used singly or in combination according to center preference. PBSC are harvested and selected for CD34+ cells. Patients under age 61 receive one of two preparative regimens: a total body irradiation (TBI)-based regimen comprising irradiation administered twice daily on days -8 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2 OR carmustine IV over 2 hours on days -6 to -4 and etoposide and cyclophosphamide as in the TBI-based regimen. Patients age 61 to 65 receive the augmented regimen comprising carmustine, etoposide, and cyclophosphamide as above. Patients receive involved field radiotherapy prior to the preparative regimen only if there is biopsy-proven residual bulk disease and at the discretion of the center. PBSC are reinfused 36-48 hours after completion of cyclophosphamide. If both bone marrow and PBSC are harvested, bone marrow is reinfused on day 0 and then PBSC are reinfused either the same day or the following day.
Patients are followed every 6 months for 2 years and then annually thereafter.
PROJECTED ACCRUAL: Approximately 360 patients (at least 135 per treatment arm) will be accrued for this study within 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004031
|Tom Baker Cancer Centre - Calgary|
|Calgary, Alberta, Canada, T2N 4N2|
|Cross Cancer Institute at University of Alberta|
|Edmonton, Alberta, Canada, T6G 1Z2|
|Winnipeg, Manitoba, Canada, R3E 0V9|
|Canada, New Brunswick|
|Moncton, New Brunswick, Canada, E1C 6Z8|
|Canada, Newfoundland and Labrador|
|Doctor H. Bliss Murphy Cancer Centre|
|St. John's, Newfoundland and Labrador, Canada, AIB 3V6|
|Canada, Nova Scotia|
|Nova Scotia Cancer Centre|
|Halifax, Nova Scotia, Canada, B3H 1V7|
|Margaret and Charles Juravinski Cancer Centre|
|Hamilton, Ontario, Canada, L8V 5C2|
|London Regional Cancer Program at London Health Sciences Centre|
|London, Ontario, Canada, N6A 4L6|
|Odette Cancer Centre at Sunnybrook|
|Toronto, Ontario, Canada, M4N 3M5|
|Hopital Du Sacre-Coeur de Montreal|
|Montreal, Quebec, Canada, H4J 1C5|
|Hopital Notre-Dame du CHUM|
|Montreal, Quebec, Canada, H2L 4M1|
|Hopital du Saint-Sacrement - Quebec|
|Quebec City, Quebec, Canada, G1S 4L8|
|Centre Hospitalier Universitaire de Quebec|
|Quebec City, Quebec, Canada, G1R 2J6|
|Saskatoon Cancer Centre at the University of Saskatchewan|
|Saskatoon, Saskatchewan, Canada, S7N 4H4|
|Study Chair:||Patrick J. Stiff, MD||Loyola University|
|Study Chair:||Thomas C. Shea, MD||UNC Lineberger Comprehensive Cancer Center|
|Study Chair:||David P. Schenkein, MD||Tufts Medical Center Cancer Center|
|Study Chair:||Stephen Couban, MD||Cancer Care Nova Scotia|