Clinical trial NCT00931918: Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients
Official title: An Open-Label, Randomized, Phase 2 Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Germinal B-Cell-like (GCB) Diffuse Large B-cell Lymphoma (DLBCL)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-07-02
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multi-center, phase 2 study of RCHOP with or without VELCADE in adult patients with previously untreated non-(Germinal B-Cell-like) GCB Diffuse Large B-cell Lymphoma (DLBCL). The study will determine whether the addition of VELCADE to RCHOP improves progression-free survival (PFS) in patients with non-GCB DLBCL.

Detailed description: The drug tested in this study is called bortezomib (VELCADE®). VELCADE® was tested in people who have Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma. This study looked at the efficacy of RCHOP \[rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone\] with or without VELCADE®.

The study enrolled 206 patients. Participants were enrolled in one of the two open label treatment groups:

* RCHOP
* Vc-RCHOP \[bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone\]

Participants received treatment for up to six, 21-day cycles.

This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 48 months. Participants made multiple visits to the clinic, and were followed for progression free survival and overall survival until patient withdrawal, death, or 2 years after the last participant was enrolled.

Eligibility criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the study:

Inclusion Criteria:

* Patients with previously untreated DLBCL that has been sub classified as the non-GCB subtype.
* At least 1 measurable tumor mass.
* Availability of paraffin block with sufficient tumor tissue.
* No evidence of central nervous system lymphoma.
* Eastern Cooperative Oncology Group (ECOG) performance status of \< or equal to 2.
* Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
* Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

Exclusion Criteria:

* Diagnosed or treated for a malignancy other than DLBCL within 2 years of first dose or evidence of active malignancy other than DLBCL.
* Peripheral neuropathy of Grade 2 or greater.
* Known history of human immunodeficiency virus (HIV) infection, unless receiving highly active antiretroviral therapy (HAART).
* Active infection requiring systemic therapy.
* Major surgery within 2 weeks before first dose.
* Patients with a left ventricular ejection fraction (LVEF) or less than 45%.
* Myocardial infarction with 6 months of enrollment or evidence of current uncontrolled cardiovascular conditions as described in the protocol.
* History of allergic reaction/ hypersensitivity attributable to boron, mannitol, polysorbate 80 or sodium citrate dehydrate, or anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab.

Primary outcomes:
measure: Progression-Free Survival (PFS) in Patients With Non-germinal Center B-cell-like (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL)
timeFrame: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm
measure: Progression-Free Survival Rate
timeFrame: 2 Years (Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm)
Secondary outcomes:
measure: Overall Survival
timeFrame: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm
measure: Overall Response Rate (ORR)
timeFrame: End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment]
measure: Complete Response Rate
timeFrame: End of Cycle 2, End of Treatment (Cycle 6) [Median of 16 weeks on treatment]
measure: Duration of Response
timeFrame: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm
measure: Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Negative Rate
timeFrame: End of Cycle 2 and End of Treatment (Cycle 6) [Median of 16 weeks on treatment]
measure: Time to Progression (TTP)
timeFrame: Median Follow-up of 34.3 months for RCHOP arm and 34.4 months for Vc-RCHOP arm
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) by Category
timeFrame: First dose of study drug through 30 days after the last dose of study drug (Up to 26 Weeks)
measure: Percentage of Participants With Chemistry and Hematology Laboratory Values Grade 3 or Higher
timeFrame: Days 1, 4 and 10 of each cycle and end of treatment visit (Median of 16 weeks on treatment)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Fountain Valley
country: United States
facility: Fountain Valley Regional Hospital
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare
state: California
city: La Jolla
country: United States
facility: Moores Cancer Center- UCSD
state: California
city: Lancaster
country: United States
facility: Antelope Valley Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: TORI- Central Pharmacy
state: California
city: Los Angeles
country: United States
facility: TORI- Central Regulatory
state: California
city: Montebello
country: United States
facility: Oncology Care Medical Associates
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group
state: California
city: Rancho Cucamonga
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: San Diego
country: United States
facility: Sharp Healthcare
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainsville
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Hollywood
country: United States
facility: Alves/ Domenech Oncology-Hematology Clinic
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute ATI
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center of Orlando
state: Florida
city: Ormond Beach
country: United States
facility: Coastal Oncology, PL
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory University
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Dublin
country: United States
facility: Dublin Hematology and Oncology
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Fishers
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: New Albany
country: United States
facility: Cancer Care Center Inc. P.C.
state: Indiana
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Care
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology and Oncology Associates LLP
state: Iowa
city: Overland Park
country: United States
facility: Kansas City Cancer Center, LLC
state: Kansas
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: St. Agnes Hospital of Baltimore
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinic Medical Center
state: Massachusetts
city: Pittsfield
country: United States
facility: Berkshie Hematology Oncology
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Lansing
country: United States
facility: Mid Michigan Physicians
state: Michigan
city: Duluth
country: United States
facility: Duluth Clinic
state: Minnesota
city: Duluth
country: United States
facility: St. Luke's Hospital Cancer Care Center
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Hematology/Oncology Associates of Northern New Jersey, P.A.
state: New Jersey
city: Mount Holly
country: United States
facility: Hematology Oncology Associates of South Jersey
state: New Jersey
city: New York
country: United States
facility: St. Luke's- Roosevelt Medical Center
state: New York
city: New York
country: United States
facility: Cornell
state: New York
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Associates P.C.
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Portland
country: United States
facility: Kaiser Group Health
state: Oregon
city: Dunmore
country: United States
facility: Hematology and Oncology Associates of NEPA
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: W Reading
country: United States
facility: Berks Hematology Oncology Associates
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Oncology Associates, PA
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Associates, PC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: US Oncology- Central Drug
state: Texas
city: Fort Worth
country: United States
facility: US Oncology- Central Laboratory
state: Texas
city: Houston
country: United States
facility: Oncology Consultants P.A.
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: The Woodlands
country: United States
facility: US Oncology- Central Regulatory
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Wichita Falls
country: United States
facility: Texoma Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Edmonds
country: United States
facility: Puget Sound Cancer Centers
state: Washington
city: Vancover
country: United States
facility: Northwest Cancer Specialists PC
state: Washington
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: