Study of VELCADE and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Phase 3

Completed

Conditions: Non-Hodgkin's Lymphoma

Interventions: Drug: Bortezomib + Rituximab
Drug: Rituximab

Registration Number: NCT00312845

Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary: The purpose of this study is to determine if the combination of VELCADE and rituximab improves progression free survival relative to rituximab alone in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (B-NHL) who never received rituximab or who have previously responded to rituximab. This is an international study being conducted in the United States and in many countries around the world. A complete list of study locations is listed below.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 676

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

Man or woman and age 18 years or older
Diagnosis of follicular B-NHL of the following subtypes (World Health Organization [WHO] classification 1997): follicular lymphoma (FL) (Grades 1 and 2).
Documented relapse or progression following prior antineoplastic treatment. New lesions or objective evidence of progression of existing lesions must document relapse or progression following the previous therapy.

If any prior regimen included rituximab, the subject must have responded (complete response [CR], unconfirmed complete response [CRu], partial response [PR]), and the time to progression (TTP) from the first dose of rituximab must have been 6 months or more.

At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis) that has not been previously irradiated, or has grown since previous irradiation
In the opinion of the investigator the decision to initiate treatment is justified to manage the subject's lymphoma
No active central nervous system lymphoma
Eastern Cooperative Oncology Group [ECOG] status ≤ 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 (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
In countries where health authorities have approved the pharmacogenomic testing, subjects or their legally acceptable representatives must have signed a separate informed consent that they agree to participate in the genetic part and protein testing part of the study; participation in the genetic and protein testing component is mandatory for pharmacogenomics testing, but optional for serum protein testing and future testing.

Exclusion Criteria

Potential subjects who meet any of the following criteria will be excluded from participating in the study:

Diagnosed or treated for a malignancy other than NHL within 1 year of randomization, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
Clinical evidence of a transformation from indolent NHL to a more aggressive form of NHL.
History of disallowed therapies:
- Prior treatment with VELCADE
- Antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization
- Nitrosoureas within 6 weeks before randomization
- Radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization
- Stem cell transplant within 6 months before randomization
- Major surgery within 2 weeks before randomization
Residual toxic effects of previous therapy or surgery of Grade 3 or worse
Peripheral neuropathy or neuropathic pain of Grade 2 or worse
Have received an experimental drug or used an experimental medical device within 21 days before the planned start of treatment.
History of allergic reaction attributable to compounds containing boron or mannitol
Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab including polysorbate 80 and sodium citrate dihydrate
Concurrent treatment with another investigational agent
Female subject who is pregnant or breast-feeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bortezomib + Rituximab	Bortezomib + Rituximab	-
Rituximab	Rituximab	-

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.	Progression free survival is defined as time from randomization to progressive disease or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months.	Overall response rate is defined as Complete Response (CR) + Complete Response Unconfirmed (CRu) + Partial Response (PR) using International Working Group Criteria (IWGC) and Independent Radiographic Review results and clinical results. The IWGC CR requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms, and normalization of lactic dehydrogenase and bone marrow involvement. CRu requires more than 75% reduction in sum of product of nodes (SPD). PR requires moer than 50% reduction in SPD.

Trial Locations

Locations (206): East Alabama Medical Center
🇺🇸
Opelika,, Alabama, United States
Central Hematology Oncology Medical Group, Inc
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Alhambra, California, United States
Comprehensive Blood and Cancer Center
🇺🇸
Bakersfield, California, United States
Providence Saint Joseph Medical Center
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Burbank, California, United States
St. Jude Heritage Medical Group
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Fullerton, California, United States
Wilshire Oncology Medical Group, Inc.
🇺🇸
La Verne, California, United States
Pacific Shores Medical Group
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Long Beach, California, United States
University of Southern California
🇺🇸
Los Angeles, California, United States
University of California, Los Angeles
🇺🇸
Los Angeles, California, United States
North Valley Hematology Oncology
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Mission Hills, California, United States
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East Alabama Medical Center
🇺🇸Opelika,, Alabama, United States