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Myfortic - Treatment for Extensive cGvHD

Primary Purpose

Graft vs Host Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Myfortic
Prednisone and Cyclosporine
Sponsored by
European Society for Blood and Marrow Transplantation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft vs Host Disease focused on measuring GvHD, graft versus host disease, extensive, myfortic

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital St. Louis
  • University Regensburg
  • Ospedale San Martino
  • University Hospital
  • Hospital Clínico Universitario
  • Karolinska University Hospital
  • University Hospital
  • University Faculty of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

Myfortic

Standard Care/ Placebo

Arm Description

Patients in this arm will receive Myfortic + Prednisone + Cyclosporine

In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine

Outcomes

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.

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.
efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity
survival without recurrent malignancy
Overall survival
cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy
the cumulative incidence of death without recurrent or malignancy

Full Information

First Posted
March 1, 2006
Last Updated
April 2, 2015
Sponsor
European Society for Blood and Marrow Transplantation
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00298324
Brief Title
Myfortic - Treatment for Extensive cGvHD
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Terminated
Why Stopped
Due to slow accrual
Study Start Date
September 2006 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
European Society for Blood and Marrow Transplantation
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft vs Host Disease
Keywords
GvHD, graft versus host disease, extensive, myfortic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Myfortic
Arm Type
Active Comparator
Arm Description
Patients in this arm will receive Myfortic + Prednisone + Cyclosporine
Arm Title
Standard Care/ Placebo
Arm Type
Other
Arm Description
In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine
Intervention Type
Drug
Intervention Name(s)
Myfortic
Intervention Description
1440mg twice daily
Intervention Type
Drug
Intervention Name(s)
Prednisone and Cyclosporine
Intervention Description
Prednisone and Cyclosporine given according to protocol. The drugs are tapered according to patient response
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity
Time Frame
1 year
Title
survival without recurrent malignancy
Time Frame
1 year
Title
Overall survival
Time Frame
1 year
Title
cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy
Time Frame
1 year
Title
the cumulative incidence of death without recurrent or malignancy
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gérard Socié
Organizational Affiliation
Hôptial St Louis, Paris
Official's Role
Study Chair
Facility Information:
Facility Name
Hopital St. Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
University Regensburg
City
Regensburg
ZIP/Postal Code
93042
Country
Germany
Facility Name
Ospedale San Martino
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
University Hospital
City
Maastricht
ZIP/Postal Code
6202
Country
Netherlands
Facility Name
Hospital Clínico Universitario
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Karolinska University Hospital
City
Huddinge
ZIP/Postal Code
141 86
Country
Sweden
Facility Name
University Hospital
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
University Faculty of Medicine
City
Ankara
ZIP/Postal Code
06260
Country
Turkey

12. IPD Sharing Statement

Links:
URL
http://ebmt.org
Description
sponsor's website

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Myfortic - Treatment for Extensive cGvHD

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