Association of Velcade to R-CHOP in the Treatment of B Cell Lymphoma

Sponsor

Lymphoma Study Association (Other)

Overall Status

Completed

CT.gov ID

NCT00169468

Collaborator

Association pour le Développement de la Recherche Clinique et Informatique en Onco-Hématologie (Other)

Enrollment

Locations

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
B Cell Lymphoma	Drug: Rituximab -CHOP plus Velcade	Phase 2

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.

Association of Velcade to standard chemotherapy regimen is under study with the aim of improving on the results.

Association of Velcade to one of the most efficient treatment of B-cell lymphoma, R-CHOP, might increase the response rate.

However, different schedules should be explored in order to better appreciate efficacy and toxicity.

This randomized phase 2 study is designed to evaluate the response rate and the toxicity of two schedules of administration of Velcade in association with R-CHOP. The aim of the study is to establish a well tolerated regimen giving a response rate in the limit upper/lower of what is observed with conventional R-CHOP used in all the different histological subtypes of B cell lymphomas patients requiring treatment.

The heterogeneity of the population will preclude any meaningful subgroup analysis.

It is important to evaluate tolerability before exploring the efficacy of this new regimen in large randomized studies or in specific phases II study which will need 50 patients for each subgroup of patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of the Association of Velcade to R-CHOP in the Treatment of B Cell Lymphoma

Actual Study Start Date :

Jan 1, 2005

Actual Primary Completion Date :

Jan 1, 2006

Actual Study Completion Date :

Jan 1, 2006

Outcome Measures

Primary Outcome Measures

Rate of complete remission [1 year]
Number of SAE [1 year]

Secondary Outcome Measures

Duration of response [1 year]
Progression free survival [1 year]
Overall survival [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Saint-Louis	Paris	Paris 10	France	75475
2	Institut Gustave Roussy	Villejuif	Villejuif Cedex	France	94805
3	Hôpital Henri Mondor	Créteil		France	94010
4	Hôpital Lyon Sud	Pierre Bénite		France	69310