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 | RxWiki

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

Overview[ - collapse ][ - ]

Purpose	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)
Condition	Diffuse Large B-Cell Lymphoma
Intervention	Drug: VELCADE Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Prednisone Drug: Vincristine
Phase	Phase 2
Sponsor	Millennium Pharmaceuticals, Inc.
Responsible Party	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier	NCT01040871
First Received	December 29, 2009
Last Updated	December 11, 2013
Last verified	December 2013

Tracking Information[ + expand ][ + ]

First Received Date	December 29, 2009
Last Updated Date	December 11, 2013
Start Date	January 2010
Estimated Primary Completion Date	August 2012
Current Primary Outcome Measures	Complete Response (CR) Rate [Time Frame: 6 cycles] [Designated as safety issue: No]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.
Current Secondary Outcome Measures	Overall Response Rate [Time Frame: 6 cycles] [Designated as safety issue: No]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 [Time Frame: Median follow up approx. 12 months] [Designated as safety issue: No]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 [Time Frame: Median follow up approx 12 months] [Designated as safety issue: No]Proportion of subjects who achieved a CR with duration of at least 6 months Subsequent Anti-lymphoma Therapy Rate at 1-year [Time Frame: 1 year] [Designated as safety issue: No]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 [Time Frame: 1 year] [Designated as safety issue: No]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 [Time Frame: 1 year] [Designated as safety issue: No]Kaplan-meier estimate of overall survival at 1-year measured from date of randomization. Change in Fatigue and Patient Utility Scores [Time Frame: 18-24 months] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

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
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)
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Diffuse Large B-Cell Lymphoma
Intervention	Drug: VELCADE VELCADE intravenous on Days 1, 4, 8, and 11 of a 21 day (3 week) cycle for 6 cycles. Drug: Rituximab Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Drug: Cyclophosphamide Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Drug: Doxorubicin Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles Drug: Prednisone Orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles Drug: Vincristine Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
Study Arm (s)	Experimental: VR-CAP 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. Active Comparator: R-CHOP 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

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	164
Estimated Completion Date	August 2012
Estimated Primary Completion Date	June 2012
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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Belgium

Administrative Information[ + expand ][ + ]

NCT Number	NCT01040871
Other Study ID Numbers	26866138-LYM-2034
Has Data Monitoring Committee	No
Information Provided By	Millennium Pharmaceuticals, Inc.
Study Sponsor	Millennium Pharmaceuticals, Inc.
Collaborators	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators	Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Verification Date	December 2013

Locations[ + expand ][ + ]