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

NCT01040871 | Completed Phase 2 Results

• 1 other identifier: 26866138-LYM-2034
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

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)

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  6 cycles

Secondary Outcomes (7)

• Overall Response Rate

  6 cycles

• Rate of Durable Response

  Median follow up approx. 12 months

• Rate of Durable Complete Response

  Median follow up approx 12 months

• Subsequent Anti-lymphoma Therapy Rate at 1-year

  1 year

• Progression-free Survival (PFS)Rate at 1-year

  1 year

Study Arms (2)

VR-CAP

EXPERIMENTAL

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; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

R-CHOP

ACTIVE COMPARATOR

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine

Interventions

VELCADE DRUG

VELCADE intravenous on Days 1, 4, 8, and 11 of a 21 day (3 week) cycle for 6 cycles.

VR-CAP

Rituximab DRUG

Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles

R-CHOP; VR-CAP

Cyclophosphamide DRUG

Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles

R-CHOP; VR-CAP

Doxorubicin DRUG

Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles

R-CHOP; VR-CAP

Prednisone DRUG

Orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles

R-CHOP; VR-CAP

Vincristine DRUG

Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles

R-CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: collaborator

Study Sites (1)

Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie

Ghent, Belgium

Location

Related Publications (1)

• 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.

  PMID: 26232170 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Bortezomib; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Helgi van de Velde
• Organization: Johnson & Johnson Pharmaceutical Research & Development

HVDVELDE@ITS.JNJ.COM

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2009
• First Posted: December 30, 2009
• Study Start: January 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: August 1, 2012
• Last Updated: January 13, 2014
• Results First Posted: November 27, 2013

Record last verified: 2013-12

Locations

BE (1)