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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT01135641
First received: June 1, 2010
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Drug: Rituximab
Drug: Ciclosporine
Drug: Corticosteroids
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of First Line Treatment of Chronic Graft Versus Host Disease With the Association of Ciclosporine, Corticosteroids and Rituximab

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Response rate at 12 months [ Designated as safety issue: No ]
    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:
  • Number of participants with adverse events as a measure of safety and tolerability [ Designated as safety issue: No ]
    To spare patients from long-term use of corticosteroids (and of their long-term side effects)

  • Treatment failure [ Designated as safety issue: No ]
    To document treatment failure-defined as initiation of another immunosuppressive agent

  • Transplant-related mortality [ Designated as safety issue: No ]
    To decrease transplant-related mortality (TRM) of infectious and non-infectious origin

  • Quality of life [ Designated as safety issue: No ]
    To improve quality of life parameters


Enrollment: 25
Study Start Date: June 2010
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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 Drug: Corticosteroids

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01135641

Locations
France
Nantes University Hospital
Nantes, France, 44093
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01135641     History of Changes
Other Study ID Numbers: 09/6-B, 2009-016898-14
Study First Received: June 1, 2010
Last Updated: April 2, 2014
Health Authority: France : AFSSAPS

Keywords provided by Nantes University Hospital:
Adult patients (≥18 years)
first allogeneic stem cell transplantation
first episode of chronic GVHD requiring systemic immunosuppressive therapy

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Immunosuppressive Agents
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 11, 2014