Combination Chemotherapy With or Without Rituximab in Non-Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabDrug: CHOP regimen
- Registration Number
- NCT00064116
- Lead Sponsor
- NCIC Clinical Trials Group
- Brief Summary
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. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating patients with non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying four different combination chemotherapy regimens and rituximab to see how well they work compared to four different combination chemotherapy regimens alone in treating patients with non-Hodgkin's lymphoma.
- Detailed Description
OBJECTIVES:
* Compare the time to treatment failure in patients with CD20-positive diffuse large B-cell non-Hodgkin's lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy with vs without rituximab.
* Compare the tumor control, progression rate, and complete remission rate in patients treated with these regimens.
* Compare the disease-free and overall survival rate of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, bulky disease (no vs yes), International Prognostic Index score (0 vs 1), and chemotherapy (CHOP vs CHOEP vs PMitCEBO vs MACOP-B). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive 1 of the following chemotherapy regimens according to participating country:
* CHOP: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone or prednisolone on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
* CHOEP-21: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
* PMitCEBO: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV on day 1; vincristine IV and bleomycin IV on day 8; and oral prednisolone daily during weeks 1-4 and every other day during week 5. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
* MACOP-B: Patients receive cyclophosphamide IV and doxorubicin IV on days 1, 15, 29, 43, 57, and 71; methotrexate IV and vincristine IV on days 8, 36, and 64; bleomycin IV and vincristine IV on days 22, 50, and 78; and oral or intramuscular prednisone on days 1-84. Treatment continues in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive arm I regimens (according to participating country) and rituximab as follows:
* CHOP and rituximab: Patients receive CHOP as in arm I and rituximab IV on day 1.
* CHOEP-21 and rituximab: Patients receive CHOEP-21 as in arm I and rituximab IV on day 1.
* PMitCEBO and rituximab: Patients receive PMitCEBO as in arm I and rituximab IV on day 1 during courses 1 and 4; on day 8 during courses 2 and 5; and on day 1 at 1 and 4 weeks after completion of the last course of PMitCEBO chemotherapy.
* MACOP-B and rituximab: Patients receive MACOP-B as in arm I and rituximab IV on days 1, 22, 43, 64, 85, and 106.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 820 patients will be accrued for this study within approximately 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 824
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm B: CHOP-21 + Rituximab rituximab Rituximab 375 mg/m² i.v. day 1\* Cyclophosphamide 750 mg/m² i.v. day 1 Doxorubicin 50 mg/m² i.v. day 1 Vincristine 2 mg (abs.) i.v. day 1 Prednisone 100 mg/d p.o. days 1 to 5 Recycle day 22 Total number of cycles: 6 Arm A: CHOP-21 CHOP regimen Cyclophosphamide 750 mg/m² i.v. day 1 Doxorubicin 50 mg/m² i.v. day 1 Vincristine 2 mg (abs.) i.v. day 1 Prednisone 100 mg/d p.o. days 1 to 5 Recycle: day 22 Total number of cycles 6 Arm B: CHOP-21 + Rituximab CHOP regimen Rituximab 375 mg/m² i.v. day 1\* Cyclophosphamide 750 mg/m² i.v. day 1 Doxorubicin 50 mg/m² i.v. day 1 Vincristine 2 mg (abs.) i.v. day 1 Prednisone 100 mg/d p.o. days 1 to 5 Recycle day 22 Total number of cycles: 6
- Primary Outcome Measures
Name Time Method Time to treatment failure (TTF) at 3 years 3 years
- Secondary Outcome Measures
Name Time Method Overall survival at 3 years 3 years Time to progression measured at 3 years 3 years Toxicity assessed by NCI CTC v2.0 after completion of treatment 3 years Complete remission rate after completion of treatment 3 years Disease-free survival (DFS) measured by TTF after an event during and directly after treatment at 3 years 3 years Progression rate determined by dividing the number of patients with disease progression by number of patients with evaluable outcome at 3 years 3 years Tumor control measured by TTF with non-tumor events censored at 3 years 3 years
Trial Locations
- Locations (25)
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
PEI Cancer Treatment Centre,Queen Elizabeth Hospital
🇨🇦Charlottetown, Prince Edward Island, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
The Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Niagara Health System
🇨🇦St. Catharines, Ontario, Canada
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
CHUM - Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
Dr. H. Bliss Murphy Cancer Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Centre hospitalier universitaire de Sherbrooke
🇨🇦Sherbrooke, Quebec, Canada
Grand River Regional Cancer Centre
🇨🇦Kitchener, Ontario, Canada
Hopital du Sacre-Coeur de Montreal
🇨🇦Montreal, Quebec, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cancer Centre of Southeastern Ontario at Kingston
🇨🇦Kingston, Ontario, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Ottawa Health Research Institute - General Division
🇨🇦Ottawa, Ontario, Canada
Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Univ. Health Network-The Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Univ. Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Trillium Health Centre - West Toronto
🇨🇦Toronto, Ontario, Canada
Hopital Charles LeMoyne
🇨🇦Greenfield Park, Quebec, Canada
McGill University - Dept. Oncology
🇨🇦Montreal, Quebec, Canada
CHA-Hopital Du St-Sacrement
🇨🇦Quebec City, Quebec, Canada
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada