Phase II Study of the Association of Velcade to R-CHOP in the Treatment of B Cell Lymphoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 48
- Locations
- 8
- Primary Endpoint
- Number of SAE
Study Overview
Brief Summary
The primary objective of this study is to evaluate the response rate and toxicity of the association R-CHOP with two schedules of administration of Velcade, in B-cell CD 20 + lymphoma patients, aged from 18 to 80 years
The goal is to get a response rate at least at what observed with R-CHOP alone and will be evaluates with a sequential test.
The other objective is to evaluate the toxicity
Detailed Description
The association of the monoclonal antibody Rituximab to chemotherapy regimen of B-cell lymphoma is associated with an increase response rate and event free survival when compared to chemotherapy alone (Coiffier et al NEJM 2002). It has been observed in almost all histological type of B-cell lymphomas. No significant increase of toxicity was observed especially in the most used regimen CHOP and the association R-CHOP is a standard for most B-cell malignancies CD20 positive.
However, in patients with diffuse large cell lymphoma progress should be made as the complete response rate is below 75% in most situation and in low grade lymphoma, although patients respond well to chemotherapy complete remission rate averaged generally 50% (Marcus et al 2003), Czuczman et al 1999) .
There is a need to improve this association with new innovative agent. Before running randomized study it is important to evaluate the like hood of getting improvement by phase 2 study testing tolerance and efficacy on a well established regimen.
Bortezomib (Velcade formerly PS 341) is a proteasome inhibitor which has shown promising activity in the treatment of refractory myeloma. As single agent in indolent lymphomas, administered twice per weeks for 2 weeks followed by one week rest period it has already showed activity in phase 2 study. It is well tolerated and main toxicity was neuropathy and thrombocytopenia.
Proteasome inhibitors can act through multiple mechanisms to arrest tumor growth, tumor spread, and angiogenesis. In vitro studies have shown a synergistic effect of the association of Velcade and doxorubicin on myeloma cell lines resistant to chemotherapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with one of the following B-cell Lymphoma CD 20 positive : Mantle cell, Marginal zone, lymphocytic, follicular requiring treatment, Histological transformation from low grade to high grade, diffuse large cell without adverse prognostic factors defined by the international prognostic index (IPI)
- •Aged from 18 to 80 years
- •Untreated with chemotherapy except with Chlorambucil or Cyclophosphamide per os alone less than 6 months
- •Previous radiotherapy except if localized
- •Performance status < 3
- •Signed inform consent
Exclusion Criteria
- •Other type of lymphomas: Burkitt, T cell, CD 20 negative
- •Central nervous system or meningeal involvement
- •Contraindication to any drug contained in the chemotherapy regimen
- •HIV disease, active hepatitis B or C
- •Treatment with polychemotherapy before except with Chlorambucil or Cyclophosphamide per os less than 6 months
- •Prior extended radiotherapy
- •Any serious active disease or co-morbid medical condition (according to investigator's decision )
- •Renal deficiency (clearance < 30 ml/mn), liver deficiency (bilirubin > 30 mmol/l) unless related to lymphoma
- •Neuropathy> grade 2 within 14 days before enrollment
- •Platelets < 30.109/l within 14 days before enrollment
- •Neutrophils < 1.0 109/l within 14 days before enrollment
- •Women with pregnancy or without adequate method of contraception
- •Any history of active cancer during the last two years
Outcomes
Primary Outcomes
Number of SAE
Time Frame: 1 year
Rate of complete remission
Time Frame: 1 year
Secondary Outcomes
- Overall survival(1 year)
- Duration of response(1 year)
- Progression free survival(1 year)