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

NCT ID: NCT00089141

Last Updated: 2013-05-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2008-09-30

Brief Summary

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.

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.

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Mycophenolate mofetil

Patients receive oral mycophenolate mofetil twice daily.

Group Type: ACTIVE_COMPARATOR

mycophenolate mofetil

Intervention Type: DRUG

Given orally

Placebo

Patients receive oral placebo twice daily

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Given orally

Interventions

mycophenolate mofetil

Given orally

Intervention Type: DRUG

placebo

Given orally

Intervention Type: DRUG

Other Intervention Names

CellCept; Control

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Martin, Paul

OTHER

Sponsor Role: lead

Responsible Party

Martin, Paul

Member

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Paul J. Martin, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Stanford Cancer Center

Stanford, California, United States

University of Florida Shands Cancer Center

Gainesville, Florida, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Oregon Health and Science University Cancer Institute

Portland, Oregon, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Baylor University Medical Center - Dallas

Dallas, Texas, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Texas Transplant Institute

San Antonio, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Washington School of Medicine

Seattle, Washington, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

Martin PJ, Storer BE, Rowley SD, Flowers ME, Lee SJ, Carpenter PA, Wingard JR, Shaughnessy PJ, DeVetten MP, Jagasia M, Fay JW, van Besien K, Gupta V, Kitko C, Johnston LJ, Maziarz RT, Arora M, Jacobson PA, Weisdorf D. Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood. 2009 May 21;113(21):5074-82. doi: 10.1182/blood-2009-02-202937. Epub 2009 Mar 6.

Reference Type: RESULT

PMID: 19270260 (View on PubMed)

Other Identifiers

FHCRC-1697.00

Identifier Type: -

Identifier Source: secondary_id

ROCHE-FHCRC-1697.00

Identifier Type: -

Identifier Source: secondary_id

UMN-2004UC007

Identifier Type: -

Identifier Source: secondary_id

CDR0000378054

Identifier Type: REGISTRY

Identifier Source: secondary_id

1697.00

Identifier Type: -

Identifier Source: org_study_id