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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00089141
• Other study ID #: 1697.00
• Secondary ID: FHCRC-1697.00ROC
• Status: Terminated
• Phase: Phase 3
• First received: August 4, 2004
• Last updated: May 1, 2013
• Start date: May 2004
• Est. completion date: September 2008

Study information

• Verified date: August 2009
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 151
• Est. completion date: September 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Graft vs Host Disease

Intervention

Drug:
• mycophenolate mofetil
Given orally
• placebo
Given orally

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Baylor University Medical Center - Dallas	Dallas	Texas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
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	Stanford Cancer Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Martin, Paul	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 f — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cure of Chronic GVHD Without Resorting to Secondary Systemic Therapy	Withdrawal of all systemic immunosuppressive treatment after resolution of chronic GVHD, before death or onset of recurrent malignancy	2 years	No
Secondary	Definitive Absence of Efficacy Success	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	No
Secondary	Open Label Systemic Treatment Because of Inadequate Response to Primary Therapy	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	No
Secondary	Bronchiolitis Obliterans	Development of bronchiolitis obliterans during treatment	within 4 years	No
Secondary	Recurrent Malignancy	Development of recurrent malignancy after enrollment in the study	within 4 years	Yes
Secondary	Non-relapse Mortality	Death without prior development of recurrent malignancy	within 4 years	Yes
Secondary	Death or Recurrent Malignancy	Death due to any cause or development of recurrent malignancy at any time after enrollment	within 4 years	Yes
Secondary	Death	Death from any cause after enrollment in the study	within 4 years	Yes
Secondary	Withdrawal of Prednisone	Withdrawal of treatment with prednisone after improvement or resolution of chronic GVHD	within 4 years	No
Secondary	End of Systemic Treatment	Withdrawal of all immunosuppressive treatment without recurrent malignancy	within 4 years	No