Myfortic - Treatment for Extensive cGvHD

Phase 3

Terminated

• Conditions: Graft vs Host Disease
• Interventions: Drug: Prednisone and Cyclosporine; Drug: Myfortic

• Registration Number: NCT00298324
• Lead Sponsor: European Society for Blood and Marrow Transplantation

Brief Summary

The purpose of this study is to determine whether the response to treatment for extensive chronic Graft versus Host Disease (cGvHD)is improved with the addition of myfortic alongside cyclosporine A and prednisone, compared to the reference treatment of cyclosporine A and prednisone alone.

Detailed Description

This clinical trial is a European, multi-center, randomized, double blinded placebo-controlled trial comparing CsA+PDN+MPA versus the reference treatment of CsA+PDN alone + placebo, in patients with extensive chronic GvHD. Randomization will be stratified according to:

* Platelet number (low versus high risk)

* Source of transplantable cells (marrow versus PBSC versus cord blood)

Patients not in progression at 6 weeks post randomization (progression defined as primary failure) will be evaluated for remission (complete or partial) at 3, 6, 9, \& 12 months post randomization

Study Timeline

• Study First Submitted: 2006-03-01
• Study First Submitted QC: 2006-03-01
• Study First Posted: 2006-03-02
• Study Start: 2006-09
• Primary Completion: 2009-11
• Study Completion: 2010-11
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-02
• Last Update Posted: 2015-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Age 18 - 60

• Any primary diagnosis requiring treatment by hematopoietic stem cell transplantation

• Recipient of a single allogeneic stem cell transplant (bone marrow or peripheral blood stem cells, or cord blood) minimum 80 days ago

• Received a graft from a related or an unrelated donor

• Conditioning regimen: Myeloablative or non-myeloablative

• Patients suffering a first episode of extensive chronic GvHD, without recurrent disease

• The diagnosis of chronic GvHD requires the following:

  • Distinction from acute GvHD
  • Presence of at least one diagnostic clinical sign of chronic GvHD or presence of at least one distinctive sign confirmed by pertinent biopsy or other relevant diagnostic tests
  • Exclusion of other possible diagnoses

• Receiving a standard prophylaxis regimen for acute GvHD: CsA plus methotrexate, or CSA+MMF for NMA, or a T-cell depleted transplant

• Patient gives written informed consent prior to randomization

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Exclusion Criteria

• Patient age less than 18 years or over 60 years.
• GvHD prophylaxis by tacrolimus plus methotrexate
• Delayed onset acute GvHD following NMA or DLI
• Second allogeneic stem cell transplant
• Not the first episode of chronic GvHD needing systemic immunosuppressive therapy.
• Limited chronic GvHD (Seattle criteria, see Appendix 1)
• Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient's death within 1 week of randomization
• In the opinion of the investigator, if the patient has significant medical or psychosocial problems or unstable disease status
• Pregnant or lactating females
• Known hypersensitivity to mycophenolic acid

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Care/ Placebo	Prednisone and Cyclosporine	In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine
Myfortic	Myfortic	Patients in this arm will receive Myfortic + Prednisone + Cyclosporine

Primary Outcome Measures

Name	Time	Method
To test whether the addition of Myfortic improves the efficacy of prednisone plus cyclosporine for treatment of newly diagnosed chronic GvHD, as defined by the proportion of patients with efficacy success at 1 year after enrollment.	1 year

Secondary Outcome Measures

Name	Time	Method
The hazard rates of efficacy success between the two arms. Loss of donor chimerism or recurrent malignancy before secondary systemic therapy and before discontinuation of all immunosuppressive meds will be treated as competing risks.	1 year
efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity	1 year
Overall survival	1 year
cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy	1 year
the cumulative incidence of death without recurrent or malignancy	1 year
survival without recurrent malignancy	1 year

Trial Locations

Locations (7)

University Regensburg; 🇩🇪 Regensburg, Germany

Hospital Clínico Universitario; 🇪🇸 Valencia, Spain

University Hospital; 🇨🇭 Basel, Switzerland

Karolinska University Hospital; 🇸🇪 Huddinge, Sweden

Hopital St. Louis; 🇫🇷 Paris, France

Ospedale San Martino; 🇮🇹 Genova, Italy

University Faculty of Medicine; 🇹🇷 Ankara, Turkey