Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma
- Conditions
- Large B Cell Lymphoma
- Interventions
- Registration Number
- NCT00118209
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.
- Detailed Description
PRIMARY OBJECTIVES:
I. To compare the event-free survival of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP) versus dose-adjusted (DA-) etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, and rituximab (EPOCH-R) chemotherapy in untreated cluster of differentiation (CD)20 positive (+) diffuse large B-cell lymphomas.
II. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling.
SECONDARY OBJECTIVES:
I. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R.
II. To define the pharmacogenomics of untreated diffuse large B-cell lymphoma (DLBCL) and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling.
III. To assess the use of molecular profiling for pathological diagnosis. IV. To identify new therapeutic targets using molecular profiling. V. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.
VI. To identify biomarkers of response to chemotherapy by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.
VII. To evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT based biomarkers of response to chemotherapy in patients with DLBCL.
VIII. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.
IX. To establish a standardized protocol for FDG-PET/CT image acquisition. X. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor maximum standard uptake value \[SUVmax\] to liver SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine physician's assessment) and evaluate their utility in refining FDG-PET/CT based biomarkers of response to therapy.
XI. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 524
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A - R-CHOP pegfilgrastim Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm A - R-CHOP cyclophosphamide Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R rituximab Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Arm A - R-CHOP rituximab Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm A - R-CHOP doxorubicin Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm A - R-CHOP vincristine Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm A - R-CHOP prednisone Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm A - R-CHOP filgrastim Patients receive the following treatment: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy * Cyclophosphamide 750 mg/m\^2 IV on Day 1 * Doxorubicin 50 mg/m\^2 IV on Day 1 * Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1 * Prednisone 40 mg/m\^2/day PO on Days 1-5 * filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R cyclophosphamide Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R doxorubicin Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R vincristine Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R etoposide Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R prednisone Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Arm B - DA-EPOCH-R filgrastim Patients receive the following treatment: Cycle 1 Doses: * Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy * Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4 * Etoposide 50 mg/m\^2/day CIVI on Days 1-4 * Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) * Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions) * Prednisone 60 mg/m\^2 PO BID on Days 1-5 * Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.
- Primary Outcome Measures
Name Time Method Progression-Free Survival Rate at 2 and 5 Years Up to 5 years post-registration Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse\>
* ≥ 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.\>
* Appearance of any new lesion during or after completion of therapy.\>
* PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.\>
The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.
- Secondary Outcome Measures
Name Time Method Response Rate Up to 5 years post-registration The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)
Overall Survival Rate at 2 and 5 Years Up to 5 years post-registration Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.
Trial Locations
- Locations (47)
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Charles R. Wood Cancer Center at Glens Falls Hospital
🇺🇸Glens Falls, New York, United States
Madigan Army Medical Center - Tacoma
🇺🇸Tacoma, Washington, United States
Marshfield Clinic at Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Geisinger Hazleton Cancer Center
🇺🇸Hazleton, Pennsylvania, United States
Easton Regional Cancer Center at Easton Hospital
🇺🇸Easton, Pennsylvania, United States
Marshfield Clinic - Indianhead Center
🇺🇸Rice Lake, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Kinston Medical Specialists
🇺🇸Kinston, North Carolina, United States
Iredell Memorial Hospital
🇺🇸Statesville, North Carolina, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Geisinger Cancer Institute at Geisinger Health
🇺🇸Danville, Pennsylvania, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Providence Cancer Institute at Providence Hospital - Southfield Campus
🇺🇸Southfield, Michigan, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
New York Weill Cornell Cancer Center at Cornell University
🇺🇸New York, New York, United States
Christian Hospital Northeast-Northwest
🇺🇸Saint Louis, Missouri, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
Camino Medical Group - Treatment Center
🇺🇸Mountain View, California, United States
Saint Helena Hospital
🇺🇸Saint Helena, California, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
🇺🇸Morgantown, West Virginia, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Marshfield Clinic - Lakeland Center
🇺🇸Minocqua, Wisconsin, United States
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Altru Cancer Center at Altru Hospital
🇺🇸Grand Forks, North Dakota, United States
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
🇺🇸Concord, New Hampshire, United States
New Hampshire Oncology - Hematology, PA - Hooksett
🇺🇸Hooksett, New Hampshire, United States
Mountainview Medical
🇺🇸Berlin, Vermont, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Naval Medical Center - San Diego
🇺🇸San Diego, California, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
Creticos Cancer Center at Advocate Illinois Masonic Medical Center
🇺🇸Chicago, Illinois, United States
National Naval Medical Center
🇺🇸Bethesda, Maryland, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
NIH - Warren Grant Magnuson Clinical Center
🇺🇸Bethesda, Maryland, United States
Mercy Cancer Center at Mercy Medical Center
🇺🇸Canton, Ohio, United States
Saint Michael's Hospital Cancer Center
🇺🇸Stevens Point, Wisconsin, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Palo Alto Medical Foundation
🇺🇸Palo Alto, California, United States