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

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ClinicalTrials.gov Identifier: NCT00089141
Recruitment Status : Terminated (Low probability of positive outcome)
First Posted : August 5, 2004
Results First Posted : August 26, 2009
Last Update Posted : May 3, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Martin, Paul, Fred Hutchinson Cancer Research Center

Study Description
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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.


Condition or disease Intervention/treatment Phase
Cancer Drug: mycophenolate mofetil Drug: placebo Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 151 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : May 2004
Actual Primary Completion Date : July 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Follicular Lymphoma Homologous Wasting Disease Ovarian Cancer Ovarian Epithelial Cancer Chronic Graft Versus Host Disease Myeloid Leukemia Chronic Myeloid Leukemia Primary Myelofibrosis Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Multiple Myeloma Neuroblastoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Childhood Acute Lymphoblastic Leukemia Marginal Zone Lymphoma Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Chronic Myeloproliferative Disorders Myelodysplastic/myeloproliferative Disease Gestational Trophoblastic Tumor Burkitt Lymphoma Chronic Neutrophilic Leukemia

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Mycophenolate mofetil
Patients receive oral mycophenolate mofetil twice daily.
 Drug: mycophenolate mofetil
Given orally
Other Name: CellCept
Placebo Comparator: Placebo
Patients receive oral placebo twice daily
 Drug: placebo
Given orally
Other Name: Control


Outcome Measures
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Primary Outcome Measures :
  1. Cure of Chronic GVHD Without Resorting to Secondary Systemic Therapy [ Time Frame: 2 years ]
    Withdrawal of all systemic immunosuppressive treatment after resolution of chronic GVHD, before death or onset of recurrent malignancy


Secondary Outcome Measures :
  1. Definitive Absence of Efficacy Success [ Time Frame: 2 years ]
    Administration of secondary systemic therapy for chronic GVHD, death during primary therapy, or onset of recurrent malignancy or bronchiolitis obliterans during primary therapy

  2. Open Label Systemic Treatment Because of Inadequate Response to Primary Therapy [ Time Frame: 2 years ]
    Administration of any systemic therapy other than the immunosuppressive agents used for initial treatment, because of persistent or progressive chronic graft-versus-host disease

  3. Bronchiolitis Obliterans [ Time Frame: within 4 years ]
    Development of bronchiolitis obliterans during treatment

  4. Recurrent Malignancy [ Time Frame: within 4 years ]
    Development of recurrent malignancy after enrollment in the study

  5. Non-relapse Mortality [ Time Frame: within 4 years ]
    Death without prior development of recurrent malignancy

  6. Death or Recurrent Malignancy [ Time Frame: within 4 years ]
    Death due to any cause or development of recurrent malignancy at any time after enrollment

  7. Death [ Time Frame: within 4 years ]
    Death from any cause after enrollment in the study

  8. Withdrawal of Prednisone [ Time Frame: within 4 years ]
    Withdrawal of treatment with prednisone after improvement or resolution of chronic GVHD

  9. End of Systemic Treatment [ Time Frame: within 4 years ]
    Withdrawal of all immunosuppressive treatment without recurrent malignancy


Eligibility Criteria
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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00089141


Locations
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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Stanford Cancer Center
Stanford, California, United States, 94305-5824
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-100277
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-3330
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
United States, Oregon
Oregon Health and Science University Cancer Institute
Portland, Oregon, United States, 97239-3098
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Texas
Baylor University Medical Center - Dallas
Dallas, Texas, United States, 75246
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
University of Washington School of Medicine
Seattle, Washington, United States, 98195
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Martin, Paul
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Paul J. Martin, MD Fred Hutchinson Cancer Research Center
More Information
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Publications of Results:

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Responsible Party: Martin, Paul, Member, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00089141    
Other Study ID Numbers: 1697.00
FHCRC-1697.00
ROCHE-FHCRC-1697.00
UMN-2004UC007
CDR0000378054 ( Registry Identifier: PDQ )
First Posted: August 5, 2004    Key Record Dates
Results First Posted: August 26, 2009
Last Update Posted: May 3, 2013
Last Verified: August 2009
Keywords provided by Martin, Paul, Fred Hutchinson Cancer Research Center:
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
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
 Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action