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

Martin, Paul

Status and phase

Terminated

Phase 3

Conditions

Cancer

Treatments

Drug: mycophenolate mofetil

Drug: placebo

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00089141

1697.00

ROCHE-FHCRC-1697.00

CDR0000378054 (Registry Identifier)

FHCRC-1697.00

UMN-2004UC007

Details and patient eligibility

About

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.

Full 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.

Enrollment

151 patients

Sex

All

Ages

4+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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