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

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.

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.

Eligibility 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