Clinical trial NCT00089141: Mycophenolate Mofetil (MMF) for Treatment of Chronic Graft-versus-host Disease (GVHD)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cancer
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
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-08-05
Enrollment: 151
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cure of Chronic GVHD Without Resorting to Secondary Systemic Therapy
timeFrame: 2 years
Secondary outcomes:
measure: Definitive Absence of Efficacy Success
timeFrame: 2 years
measure: Open Label Systemic Treatment Because of Inadequate Response to Primary Therapy
timeFrame: 2 years
measure: Bronchiolitis Obliterans
timeFrame: within 4 years
measure: Recurrent Malignancy
timeFrame: within 4 years
measure: Non-relapse Mortality
timeFrame: within 4 years
measure: Death or Recurrent Malignancy
timeFrame: within 4 years
measure: Death
timeFrame: within 4 years
measure: Withdrawal of Prednisone
timeFrame: within 4 years
measure: End of Systemic Treatment
timeFrame: within 4 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Portland
country: United States
facility: Oregon Health and Science University Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Paul J. Martin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.