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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by Lymphoma Study Association.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Association pour le Développement de la Recherche Clinique et Informatique en Onco-Hématologie
Information provided by:
Lymphoma Study Association
ClinicalTrials.gov Identifier:
NCT00169468
First received: September 13, 2005
Last updated: May 26, 2009
Last verified: May 2009
  Purpose

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 Intervention Phase
B Cell Lymphoma
Drug: Rituximab -CHOP plus Velcade
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Lymphoma Study Association:

Primary Outcome Measures:
  • Rate of complete remission
  • Toxicity

Secondary Outcome Measures:
  • Duration of response
  • Progression free survival
  • Overall survival

Estimated Enrollment: 48
Study Start Date: January 2005
Estimated Study Completion Date: August 2011
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00169468

Locations
France
Hôpital Saint-Louis
Paris, Paris 10, France, 75475
Institut Gustave Roussy
Villejuif, Villejuif Cedex, France, 94805
Hôpital Henri Mondor
Créteil, France, 94010
Hôpital Lyon Sud
Pierre Bénite, France, 69310
Sponsors and Collaborators
Lymphoma Study Association
Association pour le Développement de la Recherche Clinique et Informatique en Onco-Hématologie
Investigators
Principal Investigator: christian Gisselbrecht, MD PHD Lymphoma Study Association
  More Information

Publications:
44. Marcus R, et al. (2003). An International Multi-Centre, Randomized, Open-Label, Phase III Trial Comparing Rituximab Added to CVP Chemotherapy to CVP Chemotherapy Alone in Untreated Stage III/IV Follicular Non-Hodgkins Lymphoma. Blood, 102, issue 11, (abstract 87).
O'Connor O, Wright J, Moskowitz CH et al. Promising Activity of the Proteasome Inhibitor Bortezomib (Velcade) in the Treatment of Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma. Session Type: Poster Session 517-II. Blood, Volume 102, issue 11, November 16, 2003 (abstract 2346)

ClinicalTrials.gov Identifier: NCT00169468     History of Changes
Other Study ID Numbers: R-CHOP VELCADE
Study First Received: September 13, 2005
Last Updated: May 26, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Lymphoma Study Association:
B Lymphoma
Velcade
Chemotherapy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014