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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

Tracking Information
First Submitted Date  ICMJE August 4, 2004
First Posted Date  ICMJE August 5, 2004
Results First Submitted Date  ICMJE July 15, 2009
Results First Posted Date  ICMJE August 26, 2009
Last Update Posted Date May 3, 2013
Study Start Date  ICMJE May 2004
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2013)
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
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00089141 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2013)
  • 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
  • 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
  • Bronchiolitis Obliterans [ Time Frame: within 4 years ]
    Development of bronchiolitis obliterans during treatment
  • Recurrent Malignancy [ Time Frame: within 4 years ]
    Development of recurrent malignancy after enrollment in the study
  • Non-relapse Mortality [ Time Frame: within 4 years ]
    Death without prior development of recurrent malignancy
  • Death or Recurrent Malignancy [ Time Frame: within 4 years ]
    Death due to any cause or development of recurrent malignancy at any time after enrollment
  • Death [ Time Frame: within 4 years ]
    Death from any cause after enrollment in the study
  • Withdrawal of Prednisone [ Time Frame: within 4 years ]
    Withdrawal of treatment with prednisone after improvement or resolution of chronic GVHD
  • End of Systemic Treatment [ Time Frame: within 4 years ]
    Withdrawal of all immunosuppressive treatment without recurrent malignancy
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mycophenolate Mofetil (MMF) for Treatment of Chronic Graft-versus-host Disease (GVHD)
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: mycophenolate mofetil
    Given orally
    Other Name: CellCept
  • Drug: placebo
    Given orally
    Other Name: Control
Study Arms  ICMJE
  • Active Comparator: Mycophenolate mofetil
    Patients receive oral mycophenolate mofetil twice daily.
    Intervention: Drug: mycophenolate mofetil
  • Placebo Comparator: Placebo
    Patients receive oral placebo twice daily
    Intervention: Drug: placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 15, 2009)
151
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 2008
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00089141
Other Study ID Numbers  ICMJE 1697.00
FHCRC-1697.00
ROCHE-FHCRC-1697.00
UMN-2004UC007
CDR0000378054 ( Registry Identifier: PDQ )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Martin, Paul, Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Martin, Paul
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Paul J. Martin, MD Fred Hutchinson Cancer Research Center
PRS Account Fred Hutchinson Cancer Research Center
Verification Date August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP