Myfortic - Treatment for Extensive cGvHD

Graft vs Host Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00298324
• Other study ID #: EudraCT 2005-006178-86
• Secondary ID: EBMT-LE-0601
• Status: Terminated
• Phase: Phase 3
• First received: March 1, 2006
• Last updated: April 2, 2015
• Start date: September 2006
• Est. completion date: November 2010

Study information

• Verified date: April 2015
• Source: European Group for Blood and Marrow Transplantation
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: November 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft vs Host Disease

Intervention

Drug:
• Myfortic
1440mg twice daily
• Prednisone and Cyclosporine
Prednisone and Cyclosporine given according to protocol. The drugs are tapered according to patient response

Locations

Country	Name	City	State
France	Hopital St. Louis	Paris
Germany	University Regensburg	Regensburg
Italy	Ospedale San Martino	Genova
Netherlands	University Hospital	Maastricht
Spain	Hospital Clínico Universitario	Valencia
Sweden	Karolinska University Hospital	Huddinge
Switzerland	University Hospital	Basel
Turkey	University Faculty of Medicine	Ankara

Sponsors (2)

Lead Sponsor	Collaborator
European Group for Blood and Marrow Transplantation	Novartis

Countries where clinical trial is conducted

France,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity		1 year	Yes
Secondary	survival without recurrent malignancy		1 year	No
Secondary	Overall survival		1 year	No
Secondary	cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy		1 year	No
Secondary	the cumulative incidence of death without recurrent or malignancy		1 year	No

External Links

•   sponsor's website