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: January 21, 2014
Last verified: January 2014

October 23, 2007
January 21, 2014
October 2007
September 2013   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT00548717 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Donor stem cell engraftment, including donor-host hematopoietic chimerism studies post transplant. [ Time Frame: 1 year ]
  • The rate of renal insufficiency [ Time Frame: 1 year ]
  • To correlate the serum concentrations of mycophenolate mofetil and its metabolites with acute GVHD incidence [ Time Frame: 1 year ]
  • Incidence of 100 day mortality [ Time Frame: 100 days ]
  • Incidence of chronic GVHD [ Time Frame: 1 year ]
  • Overall survival [ Time Frame: 1 year ]
Not Provided
Not Provided
 
Sirolimus and Mycophenolate Mofetil (MMF) as Graft Versus Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Transplantation
Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Graft-vs-Host Disease
Drug: Sirolimus, MMF
Sirolimus and MMF will be used as GVHD prophylaxis
Experimental: 1
Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis
Intervention: Drug: Sirolimus, MMF
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
15
September 2013
September 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00548717
DFCI 07-197
Yes
Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
  • Wyeth is now a wholly owned subsidiary of Pfizer
  • PDL BioPharma, Inc.
Principal Investigator: Corey Cutler, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
January 2014

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