Mycophenolate Mofetil (MMF) for Treatment of Chronic Graft-versus-host Disease (GVHD)

May 1, 2013 updated by: Martin, Paul

A Randomized Study to Evaluate The Efficacy of Mycophenolate Mofetil Added to The Systemic Immunosuppressive Regimen First Used For Treatment of Chronic Graft-Versus-Host Disease

RATIONALE: Mycophenolate mofetil added to immunosuppressive treatment regimens may be effective in treating newly diagnosed chronic graft-versus-host disease caused by stem cell transplantation. It is not yet known whether immunosuppressive treatment regimens are more effective with or without mycophenolate mofetil in treating chronic graft-versus-host disease.

PURPOSE: This randomized phase III trial is studying whether the addition of mycophenolate mofetil improves the efficacy of immunosuppressive treatment regimens in patients with newly diagnosed chronic graft-versus-host disease.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the efficacy of immunosuppressive treatment regimens with vs without mycophenolate mofetil in patients with newly diagnosed chronic graft-vs-host disease.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, prospective, multicenter study. Patients are stratified according to organ involvement of chronic graft-versus-host disease (GVHD) (single organ vs multiple organs) and transplant center. Patients are randomized to 1 of 2 treatment arms.

All patients receive usual therapy for chronic GVHD comprising oral prednisone twice daily and oral cyclosporine, oral tacrolimus or oral sirolimus twice daily until 2 weeks after the first evidence of improvement of symptoms of chronic GVHD.

  • Arm I: Patients receive oral mycophenolate mofetil twice daily.
  • Arm II: Patients receive oral placebo twice daily. In both arms administration of the study drug continues for 3 months after completion of prednisone and cyclosporine, tacrolimus or sirolimus in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months.

Patients are followed every 3 months for 3-5 years.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within 3 years.

Study Type

Interventional

Enrollment (Actual)

151

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • Stanford, California, United States, 94305-5824
        • Stanford Cancer Center
    • Florida
      • Gainesville, Florida, United States, 32610-100277
        • University of Florida Shands Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0942
        • University of Michigan Comprehensive Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota
    • Nebraska
      • Omaha, Nebraska, United States, 68198-3330
        • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Oregon Health and Science University Cancer Institute
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center - Dallas
      • Houston, Texas, United States, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas
      • San Antonio, Texas, United States, 78229
        • Texas Transplant Institute
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington School of Medicine
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Newly diagnosed chronic-graft-versus host disease (GVHD)
  • Systemic immunosuppressive treatment indicated AND no contraindication to treatment with mycophenolate mofetil
  • Has undergone prior transplantation with any type of donor, hematopoietic stem cell graft, or conditioning regimen
  • No clinical, laboratory, or image-based evidence known to be present at the time of enrollment and indicating a high probability of subsequent recurrent or progressive disease

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

  • Not specified

Renal

  • Not specified

Pulmonary

  • No known bronchiolitis obliterans as a manifestation of chronic GVHD

Immunologic

  • No fungal infection without radiographic evidence of improvement during continued antifungal therapy
  • No cytomegalovirus (CMV) pneumonia without major radiographic evidence of improvement
  • No other CMV infection without reduction of antigenemia or viral load during continued antiviral therapy
  • No active disseminated varicella zoster viral infection
  • No known hypersensitivity or allergy to MMF

Gastrointestinal

  • Able to tolerate oral medication
  • No lactose-intolerant children who are too young to swallow capsules
  • No frank blood from the rectum
  • No melena
  • No known gastrointestinal ulceration

Other

  • Not pregnant or nursing
  • Negative pregnancy test

  • Fertile patients must use effective contraception

    • Female patients must use 2 forms of contraception 4 weeks prior to, during, and for 6 weeks after completion of study treatment
  • Not hospitalized at time of enrollment
  • No rare, hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics

Chemotherapy

  • Not specified

Endocrine therapy

  • Prior treatment with prednisone or equivalent allowed provided the dose was ≤ 1.0 mg/kg/day at the time of enrollment
  • Concurrent systemic glucocorticoids allowed

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • Prior mycophenolate mofetil (MMF) for prevention or treatment of acute GVHD allowed provided MMF was discontinued at least 2 weeks before the diagnosis of chronic GVHD was made
  • No prior systemic treatment for chronic GVHD
  • No prior treatment for chronic GVHD
  • Concurrent antacids allowed provided there is at least a 2-hour interval before and after administration of MMF
  • No other concurrent systemic immunosuppressive treatment except cyclosporine, tacrolimus or sirolimus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Mycophenolate mofetil
Patients receive oral mycophenolate mofetil twice daily.
Drug: mycophenolate mofetil
Given orally
Other Names:
  • CellCept
Placebo Comparator: Placebo
Patients receive oral placebo twice daily
Drug: placebo
Given orally
Other Names:
  • Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cure of Chronic GVHD Without Resorting to Secondary Systemic Therapy
Time Frame: 2 years
Withdrawal of all systemic immunosuppressive treatment after resolution of chronic GVHD, before death or onset of recurrent malignancy
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Definitive Absence of Efficacy Success
Time Frame: 2 years
Administration of secondary systemic therapy for chronic GVHD, death during primary therapy, or onset of recurrent malignancy or bronchiolitis obliterans during primary therapy
2 years
Open Label Systemic Treatment Because of Inadequate Response to Primary Therapy
Time Frame: 2 years
Administration of any systemic therapy other than the immunosuppressive agents used for initial treatment, because of persistent or progressive chronic graft-versus-host disease
2 years
Bronchiolitis Obliterans
Time Frame: within 4 years
Development of bronchiolitis obliterans during treatment
within 4 years
Recurrent Malignancy
Time Frame: within 4 years
Development of recurrent malignancy after enrollment in the study
within 4 years
Non-relapse Mortality
Time Frame: within 4 years
Death without prior development of recurrent malignancy
within 4 years
Death or Recurrent Malignancy
Time Frame: within 4 years
Death due to any cause or development of recurrent malignancy at any time after enrollment
within 4 years
Death
Time Frame: within 4 years
Death from any cause after enrollment in the study
within 4 years
Withdrawal of Prednisone
Time Frame: within 4 years
Withdrawal of treatment with prednisone after improvement or resolution of chronic GVHD
within 4 years
End of Systemic Treatment
Time Frame: within 4 years
Withdrawal of all immunosuppressive treatment without recurrent malignancy
within 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Martin, Paul

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Paul J. Martin, MD, Fred Hutchinson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

August 4, 2004

First Submitted That Met QC Criteria

August 4, 2004

First Posted (Estimate)

August 5, 2004

Study Record Updates

Last Update Posted (Estimate)

May 3, 2013

Last Update Submitted That Met QC Criteria

May 1, 2013

Last Verified

August 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1697.00
  • FHCRC-1697.00
  • ROCHE-FHCRC-1697.00
  • UMN-2004UC007
  • CDR0000378054 (Registry Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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