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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

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01040871
First received: December 29, 2009
Last updated: December 11, 2013
Last verified: December 2013
  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 Intervention Phase
Diffuse Large B-Cell Lymphoma
Drug: VELCADE
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Prednisone
Drug: Vincristine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

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.

    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.


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 ]

Enrollment: 164
Study Start Date: January 2010
Study Completion Date: August 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040871

Locations
Belgium
Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie
Gent, Belgium
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01040871     History of Changes
Obsolete Identifiers: NCT01826084
Other Study ID Numbers: 26866138-LYM-2034
Study First Received: December 29, 2009
Results First Received: July 5, 2013
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on November 19, 2014