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

NCT ID: NCT01135641

Last Updated: 2014-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-03-31

Brief Summary

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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.

Ciclosporine

Intervention Type: DRUG

Corticosteroids

Intervention Type: DRUG

Interventions

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.

Intervention Type: DRUG

Ciclosporine

Intervention Type: DRUG

Corticosteroids

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamad MOHTY, Profesor

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint-Antoine (Paris)

Noël MILPIED, Profesor

Role: STUDY_CHAIR

University Hospital, Bordeaux

Mauricette MICHALLET, Profesor

Role: STUDY_CHAIR

Hospices Civils de Lyon

Karin BILGER, Doctor

Role: STUDY_CHAIR

CHRU de Strasbourg

Oumédaly REMAN, Doctor

Role: STUDY_CHAIR

CHRU de Caen

Ibrahim YAKOUB-AGHA, Profesor

Role: STUDY_CHAIR

CHRU de Lille

Didier BLAISE, Profesor

Role: STUDY_CHAIR

Institut Paoli-Calmettes

Patrice CEBALLOS, Doctor

Role: STUDY_CHAIR

CHU de Montpellier

Patrice CHEVALLIER, Doctor

Role: STUDY_CHAIR

Nantes University Hospital

Locations

Nantes University Hospital

Nantes, , France

Countries

France

References

Malard F, Labopin M, Yakoub-Agha I, Chantepie S, Guillaume T, Blaise D, Tabrizi R, Magro L, Vanhove B, Blancho G, Moreau P, Gaugler B, Chevallier P, Mohty M. Rituximab-based first-line treatment of cGVHD after allogeneic SCT: results of a phase 2 study. Blood. 2017 Nov 16;130(20):2186-2195. doi: 10.1182/blood-2017-05-786137. Epub 2017 Sep 1.

Reference Type: DERIVED

PMID: 28864814 (View on PubMed)

Other Identifiers

2009-016898-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

09/6-B

Identifier Type: -

Identifier Source: org_study_id