Myfortic - Treatment for Extensive cGvHD

This study has been terminated.
(Due to slow accrual)
Sponsor:
Collaborator:
Novartis
Information provided by:
European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT00298324
First received: March 1, 2006
Last updated: August 26, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Graft vs Host Disease
Drug: Myfortic
Drug: Prednisone and Cyclosporine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by European Group for Blood and Marrow Transplantation:

Primary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • survival without recurrent malignancy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • the cumulative incidence of death without recurrent or malignancy [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: September 2006
Estimated Study Completion Date: November 2010
Estimated Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Myfortic
Patients in this arm will receive Myfortic + Prednisone + Cyclosporine
Drug: Myfortic
1440mg twice daily
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00298324

Locations
France
Hopital St. Louis
Paris, France, 75475
Germany
University Regensburg
Regensburg, Germany, 93042
Italy
Ospedale San Martino
Genova, Italy, 16132
Netherlands
University Hospital
Maastricht, Netherlands, 6202
Spain
Hospital Clínico Universitario
Valencia, Spain, 46010
Sweden
Karolinska University Hospital
Huddinge, Sweden, 141 86
Switzerland
University Hospital
Basel, Switzerland, 4031
Turkey
University Faculty of Medicine
Ankara, Turkey, 06260
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Novartis
Investigators
Study Chair: Gérard Socié Hôptial St Louis, Paris
  More Information

No publications provided

Responsible Party: Ruzena Uddin, EBMT
ClinicalTrials.gov Identifier: NCT00298324     History of Changes
Other Study ID Numbers: EudraCT 2005-006178-86, EBMT-LE-0601
Study First Received: March 1, 2006
Last Updated: August 26, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by European Group for Blood and Marrow Transplantation:
GvHD
graft versus host disease
extensive
myfortic

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Prednisone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014