Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients
- Conditions
- Non-Germinal B-Cell-like (GCB) Diffuse Large B-cell Lymphoma (DLBCL)
- Interventions
- Registration Number
- NCT00931918
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
This is a randomized, open-label, multi-center, phase 2 study of RCHOP with or without VELCADE in adult patients with previously untreated non-(Germinal B-Cell-like) GCB Diffuse Large B-cell Lymphoma (DLBCL). The study will determine whether the addition of VELCADE to RCHOP improves progression-free survival (PFS) in patients with non-GCB DLBCL.
- Detailed Description
The drug tested in this study is called bortezomib (VELCADE®). VELCADE® was tested in people who have Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma. This study looked at the efficacy of RCHOP \[rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone\] with or without VELCADE®.
The study enrolled 206 patients. Participants were enrolled in one of the two open label treatment groups:
* RCHOP
* Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone\]
Participants received treatment for up to six, 21-day cycles.
This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 48 months. Participants made multiple visits to the clinic, and were followed for progression free survival and overall survival until patient withdrawal, death, or 2 years after the last participant was enrolled.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 206
- Patients with previously untreated DLBCL that has been sub classified as the non-GCB subtype.
- At least 1 measurable tumor mass.
- Availability of paraffin block with sufficient tumor tissue.
- No evidence of central nervous system lymphoma.
- Eastern Cooperative Oncology Group (ECOG) performance status of < or equal to 2.
- Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
- Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Diagnosed or treated for a malignancy other than DLBCL within 2 years of first dose or evidence of active malignancy other than DLBCL.
- Peripheral neuropathy of Grade 2 or greater.
- Known history of human immunodeficiency virus (HIV) infection, unless receiving highly active antiretroviral therapy (HAART).
- Active infection requiring systemic therapy.
- Major surgery within 2 weeks before first dose.
- Patients with a left ventricular ejection fraction (LVEF) or less than 45%.
- Myocardial infarction with 6 months of enrollment or evidence of current uncontrolled cardiovascular conditions as described in the protocol.
- History of allergic reaction/ hypersensitivity attributable to boron, mannitol, polysorbate 80 or sodium citrate dehydrate, or anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RCHOP Cyclophosphamide RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. RCHOP Rituximab RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. RCHOP Doxorubicin RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. RCHOP Vincristine RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. RCHOP Prednisone RCHOP \[rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. Vc-RCHOP Bortezomib Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. Vc-RCHOP Rituximab Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. Vc-RCHOP Cyclophosphamide Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. Vc-RCHOP Doxorubicin Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. Vc-RCHOP Vincristine Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles. Vc-RCHOP Prednisone Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, prednisone\] administered as follows: bortezomib (VELCADE ®) 1.3 mg/m\^2 administered intravenous (IV) push on Days 1 and 4 of each cycle with RCHOP administered as follows: rituximab 375 mg/m\^2 intravenous (IV) infusion, cyclophosphamide 750 mg/m\^2 IV infusion, doxorubicin 50 mg/m\^2 IV injection and vincristine 1.4 mg/m\^2 (maximum total dose 2 mg) IV injection on Day 1 with prednisone orally on Days 1 through 5 of a 21-day (3-week) cycle for 6 cycles.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) in Patients With Non-germinal Center B-cell-like (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL) Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir.
Progression-Free Survival Rate 2 Years (Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm) PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause. The date of progression is the earliest date of a computed tomography/positron emission tomography (CT/PET) scan that shows evidence of PD. For a participant that has not progressed and is alive at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), PFS is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir. The progression-free survival rate is defined as the Kaplan-Meier (KM) estimate of progression-free survival at 2 years.
- Secondary Outcome Measures
Name Time Method Overall Survival Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm Overall survival is defined as the time from the date of randomization to the date of death from any cause. A participant who is alive at the end of his/her study follow-up is censored at the date of last contact.
Overall Response Rate (ORR) End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment] ORR is defined as the percentage of participants with the best overall response complete response (CR) + partial response (PR). Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. CR=disappearance of all evidence of disease and PR=regression of measurable disease and no new sites.
Complete Response Rate End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment] Complete Response Rate is defined as the percentage of participants with the best response of Complete Response (CR). Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. CR=Disappearance of all evidence of disease.
Duration of Response Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm Duration of response is defined as the time (in months) from the date of first documentation of confirmed complete response (CR) or partial response (PR) to the date of first documentation of progressive disease (PD), relapse from CR or death related to disease. For a participant who has not progressed and is not known to have died due to disease under study at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), duration of response is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using IWG-revised response criteria for malignant lymphoma. CR=Disappearance of all evidence of disease and PR=Regression of measurable disease and no new sites and PD= any new lesion or increase by \> 50% of previously involved sites from nadir.
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Negative Rate End of Cycle 2 and End of Treatment (Cycle 6) [Median of 16 weeks on treatment] FDG-PET negative rate is defined as the percentage of participants FDG-PET negative at the given time-point.
Time to Progression (TTP) Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm TTP is defined as the time from the date of randomization to the date of first documentation of progressive disease, relapse from CR, or death related to disease under study if participant did not have any documentation of disease progression prior to death caused by lymphoma or complications thereof. For a participant who has not progressed and is not known to have died due to disease under study at the end of his/her study follow-up or at the time of start of an alternate therapy (whichever is first), TTP is censored at the last overall response assessment that is stable disease or better, and which is prior to the start of the alternate therapy, if any. Disease response was assessed using International Working Group (IWG)-revised response criteria for malignant lymphoma. PD= any new lesion or increase by \> 50% of previously involved sites from nadir.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category First dose of study drug through 30 days after the last dose of study drug (Up to 26 Weeks) Percentage of participants in the following categories: • At least 1 TEAE • Drug-related, TEAEs • Grade 3 or higher TEAEs. Grade 3 are AEs of Severe Intensity • Grade 3 or higher drug-related, TEAEs • TEAEs resulting in study drug discontinuation • Serious TEAEs An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher Days 1, 4 and 10 of each cycle and end of treatment visit (Median of 16 weeks on treatment) Percentage of participants who shifted from a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 0, 1, or 2 at Baseline to a Grade 3 or higher on study (worst post-baseline grade). Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=Life-threatening consequences and 5=Death related to AE.
Trial Locations
- Locations (70)
University of Southern California
🇺🇸Los Angeles, California, United States
Winship Cancer Institute at Emory University
🇺🇸Atlanta, Georgia, United States
Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
St. Luke's Hospital Cancer Care Center
🇺🇸Duluth, Minnesota, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Lahey Clinic Medical Center
🇺🇸Burlington, Massachusetts, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Oncology Consultants P.A.
🇺🇸Houston, Texas, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Loma Linda University Cancer Center
🇺🇸Loma Linda, California, United States
Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Dublin Hematology and Oncology
🇺🇸Dublin, Georgia, United States
Cornell
🇺🇸New York, New York, United States
Antelope Valley Cancer Center
🇺🇸Lancaster, California, United States
Tower Cancer Research Foundation
🇺🇸Beverly Hills, California, United States
Alves/ Domenech Oncology-Hematology Clinic
🇺🇸Hollywood, Florida, United States
TORI- Central Pharmacy
🇺🇸Los Angeles, California, United States
Florida Cancer Institute ATI
🇺🇸New Port Richey, Florida, United States
St. Jude Heritage Healthcare
🇺🇸Fullerton, California, United States
Oncology Care Medical Associates
🇺🇸Montebello, California, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Bay Area Cancer Research Group
🇺🇸Pleasant Hill, California, United States
Wilshire Oncology Medical Group
🇺🇸Rancho Cucamonga, California, United States
Siouxland Hematology and Oncology Associates LLP
🇺🇸Sioux City, Iowa, United States
Central Indiana Cancer Centers
🇺🇸Fishers, Indiana, United States
Coastal Oncology, PL
🇺🇸Ormond Beach, Florida, United States
Cancer Care Center Inc. P.C.
🇺🇸New Albany, Indiana, United States
Mid Michigan Physicians
🇺🇸Lansing, Michigan, United States
Iowa Blood and Cancer Care
🇺🇸Cedar Rapids, Iowa, United States
Holy Cross Hospital
🇺🇸Silver Spring, Maryland, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Duluth Clinic
🇺🇸Duluth, Minnesota, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Summa Health System
🇺🇸Akron, Ohio, United States
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Hematology and Oncology Associates of NEPA
🇺🇸Dunmore, Pennsylvania, United States
Guthrie Clinic
🇺🇸Sayre, Pennsylvania, United States
Berks Hematology Oncology Associates
🇺🇸W Reading, Pennsylvania, United States
South Carolina Oncology Associates, PA
🇺🇸Columbia, South Carolina, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
US Oncology- Central Drug
🇺🇸Fort Worth, Texas, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
Kansas City Cancer Center, LLC
🇺🇸Overland Park, Kansas, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Florida Cancer Specialists & Research Institute
🇺🇸Gainsville, Florida, United States
Kaiser Group Health
🇺🇸Portland, Oregon, United States
Fountain Valley Regional Hospital
🇺🇸Fountain Valley, California, United States
Moores Cancer Center- UCSD
🇺🇸La Jolla, California, United States
TORI- Central Regulatory
🇺🇸Los Angeles, California, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
St. Agnes Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Berkshie Hematology Oncology
🇺🇸Pittsfield, Massachusetts, United States
Hematology Oncology Associates of South Jersey
🇺🇸Mount Holly, New Jersey, United States
St. Luke's- Roosevelt Medical Center
🇺🇸New York, New York, United States
Hematology/Oncology Associates of Northern New Jersey, P.A.
🇺🇸Morristown, New Jersey, United States
Chattanooga Oncology and Hematology Associates, PC
🇺🇸Chattanooga, Tennessee, United States
US Oncology- Central Laboratory
🇺🇸Fort Worth, Texas, United States
Texoma Cancer Center
🇺🇸Wichita Falls, Texas, United States
Northwest Cancer Specialists PC
🇺🇸Vancover, Washington, United States
Puget Sound Cancer Centers
🇺🇸Edmonds, Washington, United States
Raleigh Hematology Oncology Associates P.C.
🇺🇸Raleigh, North Carolina, United States
US Oncology- Central Regulatory
🇺🇸The Woodlands, Texas, United States
MD Anderson Cancer Center of Orlando
🇺🇸Orlando, Florida, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Iowa Oncology Research Association
🇺🇸Des Moines, Iowa, United States
Texas Oncology Cancer Center
🇺🇸Austin, Texas, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Sharp Healthcare
🇺🇸San Diego, California, United States