Study of First Line Treatment of Chronic Graft Versus Host Disease With the Association of Ciclosporine, Corticosteroids and Rituximab (Protocol R-GVHD) (R-GVHD)

April 2, 2014 updated by: Nantes University Hospital

Phase II Study of First Line Treatment of Chronic Graft Versus Host Disease With the Association of Ciclosporine, Corticosteroids and Rituximab

The main objective of the study is to improve the response rate (complete and partial remission) at 12 months after diagnosis of chronic Chronic Graft Versus Host Disease (GVHD) and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Nantes, France, 44093
        • Nantes University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients (≥18 years) who have received a first allogeneic stem cell transplantation for a hematological disease

  • Confirmed diagnosis of first episode of chronic GVHD requiring systemic immunosuppressive therapy. Chronic GVHD diagnosis is defined according to the NIH Working Group Consensus. Chronic GVHD diagnosis will be based on the evaluation of the severity of the different clinical manifestations including :

    1. Ocular, oral and mucosal symptoms,
    2. Performance status evaluation,
    3. Pulmonary function evaluation,
    4. Cutaneous evaluation measured by the percentage of extension of manifestations of liche-noid or sclerodermatous aspects, eventually confirmed with a biopsy whenever possible,
    5. Evaluation of the musculoskeletal manifestations, especially the amplitude of the rele-vant articulations,
    6. Evaluation of liver involvement (Total bilirubin, Transaminases, Phosphatase alcalines and Gamma GT).
  • Any source of hematopoietic stem cells is authorized.
  • Any category of conditioning regimen prior to allo-SCT is authorized.
  • Any type of stem cell donors is authorized.
  • Signed informed consent.
  • Any prior GVHD prophylaxis previously used is accepted.
  • Absence of contra-indications to the use of Rituximab.
  • Subjects affiliated with an appropriate social security system.
  • Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 3 months following the end of the study.

Exclusion Criteria:

  • Patient developing acute GVHD (whether early or "late onset" form)
  • A "limited" form of chronic GVHD not requiring systemic immunosuppressive therapy
  • Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment.
  • GVHD occurring following donor lymphocytes infusion (DLI)
  • Not the first episode of chronic GVHD needing systemic immunosuppressive therapy
  • Neutropenia <500/µL
  • Second allogeneic stem cell transplant
  • Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient's death within 1 month after the start of therapy
  • Severe neurological or psychiatric disorders
  • Denied informed consent
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab, ciclosporine and corticosteroids
As soon as the diagnosis of chronic GVHD requiring systemic immunosuppressive therapy is confirmed, patients will receive in addition to ciclosporine A and corticosteroids (prednisone) 1 mg/kg/day, Rituximab at 375 mg/m²/infusion once a week for 4 consecutive weeks.Rituximab should be administered within 14 days of starting prednisone. Follow-up dates for response assessment and laboratory tests relate to the date of Rituximab infusion.Patients having a partial response after the 1st cycle of Rituximab will be eligible to receive a second cycle of 4 infusions during 4 weeks. A delay of 8 weeks (from the first infusion of Rituximab) will be observed between the two cycles of Rituximab therapy.Patients who relapse after an initial treatment with one cycle of 4 infusions of Rituximab will be eligible to receive a second cycle of Rituximab therapy.
Drug: Corticosteroids
Drug: Rituximab
Patients will receive in addition to ciclosporine A and corticosteroids (prednisone) 1 mg/kg/day, Rituximab at 375 mg/m²/infusion once a week for 4 consecutive weeks.
Drug: Ciclosporine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Response rate at 12 months
Response rate (complete and partial remission) at 12 months after diagnosis of chronic GVHD and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Number of participants with adverse events as a measure of safety and tolerability
To spare patients from long-term use of corticosteroids (and of their long-term side effects)
Treatment failure
To document treatment failure-defined as initiation of another immunosuppressive agent
Transplant-related mortality
To decrease transplant-related mortality (TRM) of infectious and non-infectious origin
Quality of life
To improve quality of life parameters

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Investigators

  • Principal Investigator: Mohamad MOHTY, Profesor, Hôpital Saint-Antoine (Paris)
  • Study Chair: Noël MILPIED, Profesor, University Hospital, Bordeaux
  • Study Chair: Mauricette MICHALLET, Profesor, Chu de Lyon
  • Study Chair: Karin BILGER, Doctor, CHRU de Strasbourg
  • Study Chair: Oumédaly REMAN, Doctor, CHRU de Caen
  • Study Chair: Ibrahim YAKOUB-AGHA, Profesor, CHRU de Lille
  • Study Chair: Didier BLAISE, Profesor, Institut Paoli-Calmettes
  • Study Chair: Patrice CEBALLOS, Doctor, CHU de Montpellier
  • Study Chair: Patrice CHEVALLIER, Doctor, CHU de Nantes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

June 1, 2010

First Submitted That Met QC Criteria

June 2, 2010

First Posted (Estimate)

June 3, 2010

Study Record Updates

Last Update Posted (Estimate)

April 3, 2014

Last Update Submitted That Met QC Criteria

April 2, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09/6-B
  • 2009-016898-14 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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