Mycophenolate Mofetil (MMF) for Treatment of Chronic Graft-versus-host Disease (GVHD)
Condition: Cancer
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: mycophenolate mofetil; placebo
Intervention description: Given orally; Given orally
Intervention MeSH terms: Mycophenolic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 151.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: graft versus host disease; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; atypical chronic myeloid leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; chronic eosinophilic leukemia; chronic idiopathic myelofibrosis; chronic myelomonocytic leukemia; chronic neutrophilic leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; disseminated neuroblastoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; juvenile myelomonocytic leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; nodal marginal zone B-cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; poor prognosis metastatic gestational trophoblastic tumor; previously treated childhood rhabdomyosarcoma; previously treated myelodysplastic syndromes; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; splenic marginal zone lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage II ovarian epithelial cancer; stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III chronic lymphocytic leukemia; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III multiple myeloma; stage III ovarian epithelial cancer; stage III small lymphocytic lymphoma; stage III malignant testicular germ cell tumor; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV breast cancer; stage IV chronic lymphocytic leukemia; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV ovarian epithelial cancer; stage IV small lymphocytic lymphoma; childhood myelodysplastic syndromes

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.
    

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