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
4 Years
N/A
Both
Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
Cure of Chronic GVHD Without Resorting to Secondary Systemic Therapy
Outcome Description:
Withdrawal of all systemic immunosuppressive treatment after resolution of chronic GVHD, before death or onset of recurrent malignancy
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Paul J. Martin, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Food and Drug Administration
Study ID:
1697.00
NCT ID:
NCT00089141
Start Date:
May 2004
Completion Date:
September 2008
Related Keywords:
- Cancer
- 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
- Graft vs Host Disease
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
| M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
| University of Washington School of Medicine | Seattle, Washington 98195 |
| Stanford Cancer Center | Stanford, California 94305-5824 |
| Texas Transplant Institute | San Antonio, Texas 78229 |
| Oregon Health and Science University Cancer Institute | Portland, Oregon 97239-3098 |
| Baylor University Medical Center - Dallas | Dallas, Texas 75246 |
