Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximab
- Registration Number
- NCT00078949
- Lead Sponsor
- NCIC Clinical Trials Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation. Rituximab was added to both salvage treatment arms for CD20+ patients in a protocol amendment in 2005.
- Detailed Description
OBJECTIVES:
Salvage therapy
Primary
* Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with or without rituximab).
* To compare the transplantation rates of the two protocol salvage regimens.
Secondary
* Compare the event-free and overall survival of patients treated with these regimens.
* Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy.
* Compare the quality of life of patients treated with these salvage regimens.
* Compare the toxic effects of these salvage regimens in these patients.
* Compare resource utilization for patients treated with these salvage regimens.
* Compare relative medical and societal costs of these salvage regimens with outcomes in these patients.
Maintenance therapy
Primary
* Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment.
Secondary
* Compare the 2-year survival of patients treated with or without maintenance rituximab.
* Compare the toxic effects of rituximab vs observation alone in these patients.
OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are stratified according to participating center, International Prognostic Index score at relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or response duration after initial chemotherapy (no response or progressive disease vs \> 1 year vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are stratified according to participating center, salvage therapy treatment randomization (with or without rituximab, cisplatin, dexamethasone, and gemcitabine vs with or without rituximab, cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response \[CR\] and CR unconfirmed \[CRu\] vs partial response \[PR\] vs stable disease \[SD\]), and prior rituximab (yes vs no).
* Salvage therapy: Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.
* Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.
In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Patients are reassessed after 2 courses. Patients with progressive disease are removed from study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT). Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator. Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy. Patients with progressive disease are removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator.
* ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation.
* Maintenance therapy: Patients are randomized to 1 of 2 treatment arms.
* Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation.
Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter.
PROJECTED ACCRUAL: A total of 637 patients will be accrued for this study within 3-4 years for the first randomization, and 240 transplanted CD20+ patients will be needed for the second randomization.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 849
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Salvage arm I gemcitabine hydrochloride Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Salvage arm II cytarabine Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Maintenance arm I rituximab Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. Salvage arm I cisplatin Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Salvage arm I dexamethasone Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Salvage arm II cisplatin Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Salvage arm II dexamethasone Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2.
- Primary Outcome Measures
Name Time Method Response Rate of Patients After 2 Courses of Chemotherapy After 2 cycle of treatment The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).
Transplantation Rate of Patients After 2 Courses of Chemotherapy During period 1 (salvage chemotherapy) Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients
Event-free Survival of Patients on Maintenance Randomization (Period 2) during the period 2 (up to10 years) Number of patients who develop EFS event during maintenance randomization (period 2)
- Secondary Outcome Measures
Name Time Method Toxic Effect 48 months Number of patients affected by adverse events graded according to CTC Version 2.0. See adverse event (others) for details.
Trial Locations
- Locations (27)
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Rush-Presbyterian-St. Luke's Medical Centre
🇺🇸Chicago, Illinois, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Credit Valley Hospital
🇨🇦Mississauga, Ontario, Canada
Univ. Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Thunder Bay Regional Health Science Centre
🇨🇦Thunder Bay, Ontario, Canada
CHA-Hopital Du St-Sacrement
🇨🇦Quebec City, Quebec, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
The Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
University of Cincinnati, Barrett Cancer Centre
🇺🇸Cincinnati, Ohio, United States
Cancer Centre of Southeastern Ontario at Kingston
🇨🇦Kingston, Ontario, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Dr. H. Bliss Murphy Cancer Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hopital Charles LeMoyne
🇨🇦Greenfield Park, Quebec, Canada
Centre hospitalier universitaire de Sherbrooke
🇨🇦Sherbrooke, Quebec, Canada
The Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
CHUM - Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
CHUQ-Pavillon Hotel-Dieu de Quebec
🇨🇦Quebec City, Quebec, Canada
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada