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

Primary Purpose

Graft Versus Host Disease

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Rituximab

Ciclosporine

Corticosteroids

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring Adult patients (≥18 years), first allogeneic stem cell transplantation, first episode of chronic GVHD requiring systemic immunosuppressive therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Nantes University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab, ciclosporine and corticosteroids

Arm Description

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.

Outcomes

Primary Outcome Measures

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

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

Full Information

NCT ID

NCT01135641

First Posted

June 1, 2010

Last Updated

April 2, 2014

Sponsor

Nantes University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01135641

Brief Title

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

Acronym

R-GVHD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

June 2010 (undefined)

Primary Completion Date

March 2014 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nantes University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft Versus Host Disease

Keywords

Adult patients (≥18 years), first allogeneic stem cell transplantation, first episode of chronic GVHD requiring systemic immunosuppressive therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rituximab, ciclosporine and corticosteroids

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Description

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

Intervention Name(s)

Ciclosporine

Intervention Type

Drug

Intervention Name(s)

Corticosteroids

Primary Outcome Measure Information:

Title

Response rate at 12 months

Description

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 Measure Information:

Title

Number of participants with adverse events as a measure of safety and tolerability

Description

To spare patients from long-term use of corticosteroids (and of their long-term side effects)

Title

Treatment failure

Description

To document treatment failure-defined as initiation of another immunosuppressive agent

Title

Transplant-related mortality

Description

To decrease transplant-related mortality (TRM) of infectious and non-infectious origin

Title

Quality of life

Description

To improve quality of life parameters

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 : Ocular, oral and mucosal symptoms, Performance status evaluation, Pulmonary function evaluation, Cutaneous evaluation measured by the percentage of extension of manifestations of liche-noid or sclerodermatous aspects, eventually confirmed with a biopsy whenever possible, Evaluation of the musculoskeletal manifestations, especially the amplitude of the rele-vant articulations, 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

Overall Study Officials: