Sirolimus and Mycophenolate Mofetil (MMF) as Graft Versus Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Transplantation
This study is currently recruiting participants.
Verified June 2013 by Dana-Farber Cancer Institute
Sponsor:
Dana-Farber Cancer Institute
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: June 10, 2013
Last verified: June 2013
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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:
MedlinePlus related topics:
Cancer
Drug Information available for:
Mycophenolic acid
Mycophenolate sodium
Sirolimus
Mycophenolate mofetil hydrochloride
Mycophenolate mofetil
Everolimus
Temsirolimus
U.S. FDA Resources
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: | 43 |
| Study Start Date: | October 2007 |
| Estimated Study Completion Date: | January 2015 |
| Estimated Primary Completion Date: | January 2015 (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:
- 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
Contacts
| Contact: Corey Cutler, MD | 617-632-4719 | corey_cutler@dfci.harvard.edu |
Locations
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Principal Investigator: Corey Cutler, MD | |
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: | June 10, 2013 |
| 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 June 18, 2013