SWOG-9704 Chemoradiotherapy and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabDrug: CHOP regimenProcedure: bone marrow ablation with stem cell supportProcedure: peripheral blood stem cell transplantationRadiation: radiation therapy
- Registration Number
- NCT00004031
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 397
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CHOP/CHOP-R x 3 rituximab 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 CHOP/CHOP-R x 3 CHOP regimen 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 CHOP/CHOP-R x 3 vincristine sulfate 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 CHOP/CHOP-R x 3 bone marrow ablation with stem cell support 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 CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant rituximab 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant CHOP regimen 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant vincristine sulfate 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant bone marrow ablation with stem cell support 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant radiation therapy 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant peripheral blood stem cell transplantation 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. CHOP/CHOP-R x 3 cyclophosphamide 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 CHOP/CHOP-R x 3 doxorubicin hydrochloride 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 CHOP/CHOP-R x 3 prednisone 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 CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant doxorubicin hydrochloride 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant carmustine 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant cyclophosphamide 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant etoposide 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. CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant prednisone 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.
- Primary Outcome Measures
Name Time Method 2-year Overall Survival Rates up to 2 years post registration Percentage of participants surviving 2 years post registration
2 Year Progression-free Survival From registration until death Percentage of participants without disease progression up to 2 years post-registration.
- Secondary Outcome Measures
Name Time Method Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Duration of treatment and follow up until death or 3 years post registration Adverse Events (AEs) are reported by CTCAE Version 2.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Higher grades indicate higher severity of adverse events.
Trial Locations
- Locations (15)
Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec City, Quebec, Canada
Cross Cancer Institute at University of Alberta
🇨🇦Edmonton, Alberta, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Hopital Notre-Dame du CHUM
🇨🇦Montreal, Quebec, Canada
Margaret and Charles Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Nova Scotia Cancer Centre
🇨🇦Halifax, Nova Scotia, Canada
Hopital Du Sacre-Coeur de Montreal
🇨🇦Montreal, Quebec, Canada
Hopital du Saint-Sacrement - Quebec
🇨🇦Quebec City, Quebec, Canada
London Regional Cancer Program at London Health Sciences Centre
🇨🇦London, Ontario, Canada
Odette Cancer Centre at Sunnybrook
🇨🇦Toronto, Ontario, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
Doctor H. Bliss Murphy Cancer Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Tom Baker Cancer Centre - Calgary
🇨🇦Calgary, Alberta, Canada