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

This study has been terminated.
(First two patients enrolled after trial reopened, developed grade III-IV acute GVHD and subsequently passed away.)
Sponsor:
Collaborators:
Wyeth is now a wholly owned subsidiary of Pfizer
PDL BioPharma, Inc.
Information provided by (Responsible Party):
Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00548717
First received: October 23, 2007
Last updated: July 18, 2014
Last verified: July 2014
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

Resource links provided by NLM:


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 ]

Enrollment: 15
Study Start Date: October 2007
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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:

  1. Patients with hematologic malignancies, who are at high risk of complications after conventional myeloablative transplantation
  2. 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
  3. Patient age greater than 18
  4. Performance status 0-2
  5. Life expectancy of > 100 days without transplantation
  6. Written informed consent must be obtained in all cases from the patient

Exclusion Criteria:

  1. Pregnancy
  2. Prior Allogeneic Stem Cell Transplantation from any donor
  3. Evidence of HIV infection or active Hepatitis B or C infection
  4. Heart failure uncontrolled by medications
  5. Total bilirubin > 2.0 mg/dl that is due to hepatocellular dysfunction
  6. AST > 90
  7. Cholesterol > 300 mg/dl or Triglycerides > 400 mg/dl while adequately treated
  8. Uncontrolled bacterial, viral or fungal infection
  9. Requirement for voriconazole at the time of hospital admission
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 is now a wholly owned subsidiary of Pfizer
PDL BioPharma, Inc.
Investigators
Principal Investigator: Corey Cutler, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Corey S. Cutler, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00548717     History of Changes
Other Study ID Numbers: DFCI 07-197
Study First Received: October 23, 2007
Last Updated: July 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
GVHD
Stem cell transplantation
Sirolimus

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Mycophenolate mofetil
Sirolimus
Everolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 22, 2014