Myfortic - Treatment for Extensive cGvHD

Sponsor

European Society for Blood and Marrow Transplantation (Other)

Overall Status

Terminated

CT.gov ID

NCT00298324

Collaborator

Novartis (Industry)

Enrollment

Locations

Arms

Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

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

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Nov 1, 2010

Arms and Interventions

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

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

Outcome Measures

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. [1 year]

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. [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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital St. Louis	Paris	France	75475
2	University Regensburg	Regensburg	Germany	93042
3	Ospedale San Martino	Genova	Italy	16132
4	University Hospital	Maastricht	Netherlands	6202
5	Hospital Clínico Universitario	Valencia	Spain	46010
6	Karolinska University Hospital	Huddinge	Sweden	141 86
7	University Hospital	Basel	Switzerland	4031
8	University Faculty of Medicine	Ankara	Turkey	06260