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

Millennium Pharmaceuticals, Inc.164 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

164

Conditions

Diffuse Large B-Cell Lymphoma

Interventions

VELCADEDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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. 1. Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. PET scan was negative. 3. 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. 4. If bone marrow was involved before treatment, the infiltrate cleared on repeated bone marrow biopsy. 5. No new sites of disease were detected.

Time frame: 6 cycles

Secondary Outcomes

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.

Time frame: 6 cycles

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.

Time frame: Median follow up approx. 12 months

Rate of Durable Complete Response

Proportion of subjects who achieved a CR with duration of at least 6 months

Time frame: Median follow up approx 12 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.

Time frame: 1 year

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.

Time frame: 1 year

Overall Survival Rate at 1-year

Kaplan-meier estimate of overall survival at 1-year measured from date of randomization.

Time frame: 1 year

Change in Fatigue and Patient Utility Scores

Time frame: 18-24 months

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

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes