Back to resultsStudy of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
Primary Purpose
Diffuse Large B-Cell Lymphoma
Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
VELCADE
Rituximab
Cyclophosphamide
Doxorubicin
Prednisone
Vincristine
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Male or female patients 18 years or older.
- Newly Diagnosed non-GCB subtype of DLBCL (Stage II, III or IV).
- At least 1 measurable site of disease.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; and have a negative pregnancy test at screening.
- Male subjects must agree to use a double barrier method of birth control
Exclusion Criteria:
- Prior treatment with VELCADE.
- Prior extended radiotherapy or chemotherapy for lymphoma
- More than 150 mg/m2 of prior doxorubicin
- Major surgery within 3 weeks of study.
- Peripheral neuropathy or neuralgia of Grade 2 or worse.
- Active CNS lymphoma
- Diagnosed or treated for a malignancy other than NHL, with some exceptions
- Pregnant or breast feeding
- Active systemic infection
- Documented of suspected human immunodeficiency virus (HIV)/AIDS
- Uncontrolled or severe cardiovascular disease
- Known allergies, hypersensitivity or intolerance to study drugs
- Serious medical condition that could interfere with study
- Concurrent treatment with another investigational agent
Sites / Locations
- Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
VR-CAP
R-CHOP
Arm Description
VR-CAP arm received rituximab 375 mg/m2 IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, VELCADE 1.3 mg/m2 IV on Days 1, 4, 8, and 11, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles.
R-CHOP received rituximab 375 mg/m2IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, vincristine 1.4 mg/m2 (maximum total of 2 mg) IV on Day 1, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles.Prednisone
Outcomes
Primary Outcome Measures
Complete Response (CR) Rate
Complete response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
PET scan was negative.
The spleen and/or liver, if enlarged before therapy on the basis of physical examination or CT scan, was not palpable on physical examination and was considered normal size by imaging studies; all splenic and hepatic nodules related to lymphomas disappeared.
If bone marrow was involved before treatment, the infiltrate cleared on repeated bone marrow biopsy.
No new sites of disease were detected.
Secondary Outcome Measures
Overall Response Rate
Overall response = Complete Response (CR) + Partial Response (PR) Response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Complete Response: see primary endpoint Partial Response: At least a 50% decrease in the sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
Rate of Durable Response
Proportion of subjects who achieved a CR or PR with duration of at least 6 months. Duration of response (CR or PR) was calculated from the date of initial documentation of a response to the date of first documented evidence of disease progression or death due to disease progression. Response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Rate of Durable Complete Response
Proportion of subjects who achieved a CR with duration of at least 6 months
Subsequent Anti-lymphoma Therapy Rate at 1-year
Kaplan-meier estimate of subsequent anti-lymphoma therapy at 1-year. Time to subsequent anti-lymphoma therapy was measured from the date of randomization to the start date of new treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, time to next anti-lymphoma treatment was censored at the date of death or the last date known to be alive.
Progression-free Survival (PFS)Rate at 1-year
Kaplan-meier estimate of progression-free survival at 1-year. Progression-free survival was defined as the interval between the date of randomization and the date of first documented evidence of disease progression or death.
Overall Survival Rate at 1-year
Kaplan-meier estimate of overall survival at 1-year measured from date of randomization.
Change in Fatigue and Patient Utility Scores
Full Information
NCT ID
NCT01040871
First Posted
December 29, 2009
Last Updated
December 11, 2013
Sponsor
Millennium Pharmaceuticals, Inc.
Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
1. Study Identification
Unique Protocol Identification Number
NCT01040871
Brief Title
Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
Official Title
A Randomized, Open-Label, Multicenter Phase 2 Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, open-label, active-control, parallel-group, multicenter, multinational Phase 2 Study of the efficacy and safety of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Patients With Newly Diagnosed Non-Germinal Center B-Cell (non-GCB) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
164 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VR-CAP
Arm Type
Experimental
Arm Description
VR-CAP arm received rituximab 375 mg/m2 IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, VELCADE 1.3 mg/m2 IV on Days 1, 4, 8, and 11, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles.
Arm Title
R-CHOP
Arm Type
Active Comparator
Arm Description
R-CHOP received rituximab 375 mg/m2IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, vincristine 1.4 mg/m2 (maximum total of 2 mg) IV on Day 1, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles.Prednisone
Intervention Type
Drug
Intervention Name(s)
VELCADE
Intervention Description
VELCADE intravenous on Days 1, 4, 8, and 11 of a 21 day (3 week) cycle for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
Primary Outcome Measure Information:
Title
Complete Response (CR) Rate
Description
Complete response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
PET scan was negative.
The spleen and/or liver, if enlarged before therapy on the basis of physical examination or CT scan, was not palpable on physical examination and was considered normal size by imaging studies; all splenic and hepatic nodules related to lymphomas disappeared.
If bone marrow was involved before treatment, the infiltrate cleared on repeated bone marrow biopsy.
No new sites of disease were detected.
Time Frame
6 cycles
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Overall response = Complete Response (CR) + Partial Response (PR) Response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Complete Response: see primary endpoint Partial Response: At least a 50% decrease in the sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
Time Frame
6 cycles
Title
Rate of Durable Response
Description
Proportion of subjects who achieved a CR or PR with duration of at least 6 months. Duration of response (CR or PR) was calculated from the date of initial documentation of a response to the date of first documented evidence of disease progression or death due to disease progression. Response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Time Frame
Median follow up approx. 12 months
Title
Rate of Durable Complete Response
Description
Proportion of subjects who achieved a CR with duration of at least 6 months
Time Frame
Median follow up approx 12 months
Title
Subsequent Anti-lymphoma Therapy Rate at 1-year
Description
Kaplan-meier estimate of subsequent anti-lymphoma therapy at 1-year. Time to subsequent anti-lymphoma therapy was measured from the date of randomization to the start date of new treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, time to next anti-lymphoma treatment was censored at the date of death or the last date known to be alive.
Time Frame
1 year
Title
Progression-free Survival (PFS)Rate at 1-year
Description
Kaplan-meier estimate of progression-free survival at 1-year. Progression-free survival was defined as the interval between the date of randomization and the date of first documented evidence of disease progression or death.
Time Frame
1 year
Title
Overall Survival Rate at 1-year
Description
Kaplan-meier estimate of overall survival at 1-year measured from date of randomization.
Time Frame
1 year
Title
Change in Fatigue and Patient Utility Scores
Time Frame
18-24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients 18 years or older.
Newly Diagnosed non-GCB subtype of DLBCL (Stage II, III or IV).
At least 1 measurable site of disease.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; and have a negative pregnancy test at screening.
Male subjects must agree to use a double barrier method of birth control
Exclusion Criteria:
Prior treatment with VELCADE.
Prior extended radiotherapy or chemotherapy for lymphoma
More than 150 mg/m2 of prior doxorubicin
Major surgery within 3 weeks of study.
Peripheral neuropathy or neuralgia of Grade 2 or worse.
Active CNS lymphoma
Diagnosed or treated for a malignancy other than NHL, with some exceptions
Pregnant or breast feeding
Active systemic infection
Documented of suspected human immunodeficiency virus (HIV)/AIDS
Uncontrolled or severe cardiovascular disease
Known allergies, hypersensitivity or intolerance to study drugs
Serious medical condition that could interfere with study
Concurrent treatment with another investigational agent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie
City
Gent
Country
Belgium
12. IPD Sharing Statement
Citations:
PubMed Identifier
26232170
Citation
Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. doi: 10.1182/blood-2015-03-632430. Epub 2015 Jul 31.
Results Reference
derived
Learn more about this trial
Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
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