Sirolimus and Mycophenolate Mofetil (MMF) as Graft Versus Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Transplantation - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute Wyeth PDL BioPharma, Inc.
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00548717

Purpose

This trial will test the hypothesis that the combination of sirolimus and mycophenolate mofetil will be effective in preventing both acute and chronic GVHD after reduced intensity allogeneic stem cell transplantation.

Condition	Intervention	Phase
Graft-vs-Host Disease	Drug: Sirolimus, MMF	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Sirolimus Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To determine the rate of Grade II-IV acute GVHD when the combination of sirolimus and mycophenolate mofetil is used for GVHD prophylaxis after allogeneic stem cell transplantation in patients with hematologic malignancies [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Donor stem cell engraftment, including donor-host hematopoietic chimerism studies post transplant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The rate of renal insufficiency [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To correlate the serum concentrations of mycophenolate mofetil and its metabolites with acute GVHD incidence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Incidence of 100 day mortality [ Time Frame: 100 days ] [ Designated as safety issue: No ]
Incidence of chronic GVHD [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2007
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis	Drug: Sirolimus, MMF Sirolimus and MMF will be used as GVHD prophylaxis

Detailed Description:

The combination of tacrolimus and methotrexate is standard therapy for prevention of GVHD, however, our recent experience has demonstrated that the substitution of sirolimus for methotrexate provides superior GVHD control with reduced transplant-related toxicity. One limitation to the use of calcineurin inhibitors in GVHD prevention is the disruption in Treg function and proliferation. Based on our evolving understanding of the role of Treg in the development of chronic GVHD, we propose a GVHD prophylactic regimen that is effective in prevention of acute GVHD, but by virtue of the maintenance of Treg activity may be able to prevent chronic GVHD. We hypothesize that the substitution of mycophenolate mofetil for tacrolimus may provide similar protection against acute GVHD and prevent chronic GVHD while minimizing renal toxicity after transplantation.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with hematologic malignancies, who are at high risk of complications after conventional myeloablative transplantation
Patients must have a 6/6 matched, related donor. Matching at HLA Class II will be based on PCR of sequence specific primers (SSP). Among family member transplants, serologic matching at Class I is sufficient
Patient age greater than 18
Performance status 0-2
Life expectancy of > 100 days without transplantation
Written informed consent must be obtained in all cases from the patient

Exclusion Criteria:

Pregnancy
Prior Allogeneic Stem Cell Transplantation from any donor
Evidence of HIV infection or active Hepatitis B or C infection
Heart failure uncontrolled by medications
Total bilirubin > 2.0 mg/dl that is due to hepatocellular dysfunction
AST > 90
Cholesterol > 300 mg/dl or Triglycerides > 400 mg/dl while adequately treated
Uncontrolled bacterial, viral or fungal infection
Requirement for voriconazole at the time of hospital admission

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548717

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

Wyeth

PDL BioPharma, Inc.

Investigators

Principal Investigator:

Corey Cutler, MD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Dana-Farber Cancer Institute ( Corey Cutler, MD )
Study ID Numbers:	DFCI 07-197
Study First Received:	October 23, 2007
Last Updated:	March 13, 2009
ClinicalTrials.gov Identifier:	NCT00548717 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

GHD
Stem cell transplantation
Sirolimus

Study placed in the following topic categories:

Sirolimus
Graft Versus Host Disease
Anti-Bacterial Agents
Immunologic Factors
Clotrimazole
Miconazole

Antifungal Agents
Tioconazole
Mycophenolate mofetil
Graft vs Host Disease
Immunosuppressive Agents
Homologous Wasting Disease

Additional relevant MeSH terms:

Sirolimus
Anti-Infective Agents
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic

Immunosuppressive Agents
Pharmacologic Actions
Anti-Bacterial Agents
Therapeutic Uses
Antifungal Agents
Mycophenolate mofetil
Graft vs Host Disease

ClinicalTrials.gov processed this record on May 07, 2009