Myfortic - Treatment for Extensive cGvHD

A Randomized Double Blinded Placebo-Controlled Phase III Trial Comparing Cyclosporine Plus Steroids With or Without Myfortic as Primary Treatment for Extensive Chronic Graft Versus Host Disease

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.

Study Overview

• Status: Terminated
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Drug: Myfortic; Drug: Prednisone and Cyclosporine

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75475
    • Hopital St. Louis
• Germany
  • Regensburg, Germany, 93042
    • University Regensburg
• Italy
  • Genova, Italy, 16132
    • Ospedale San Martino
• Netherlands
  • Maastricht, Netherlands, 6202
    • University Hospital
• Spain
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario
• Sweden
  • Huddinge, Sweden, 141 86
    • Karolinska University Hospital
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital
• Turkey
  • Ankara, Turkey, 06260
    • University Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Myfortic; Patients in this arm will receive Myfortic + Prednisone + Cyclosporine	Drug: Myfortic; 1440mg twice daily
Other: Standard Care/ Placebo; In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine	Drug: Prednisone and Cyclosporine; Prednisone and Cyclosporine given according to protocol. The drugs are tapered according to patient response

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Overall survival	1 year
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
survival without recurrent malignancy	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

Collaborators and Investigators

• Sponsor: European Society for Blood and Marrow Transplantation
• Collaborators: Novartis
• Investigators: Study Chair: Gérard Socié, Hôptial St Louis, Paris

Publications and helpful links

Helpful Links

• sponsor's website

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: March 1, 2006
• First Submitted That Met QC Criteria: March 1, 2006
• First Posted (Estimate): March 2, 2006

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: April 2, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: GvHD; graft versus host disease; extensive; myfortic
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Prednisone; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: EudraCT 2005-006178-86; EBMT-LE-0601