Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

This study has been terminated.
(Low accrual)
Sponsor:
Information provided by (Responsible Party):
Stuart Seropian, Yale University
ClinicalTrials.gov Identifier:
NCT00623012
First received: February 13, 2008
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

The objective of this study is to evaluate feasibility, toxicity and efficacy of using Rapamycin to prevent chronic graft-versus-host-disease (GVHD) during and after the tacrolimus taper in recipients of allogeneic stem cell transplant.

Our hypothesis is that the T cells that can cause chronic GVHD are suppressed but not eliminated by calcineurin inhibitors. Therefore, when the calcineurin inhibitors are discontinued, the T cells may get activated and result in GVHD. Rapamycin on the other hand will allow anergy formation and thus when discontinued, T cells should not get activated. The schedule is designed to have therapeutic rapamycin levels as the tacrolimus is discontinued. Rapamycin will be continued as a single agent for additional 4 weeks and be tapered off in two weeks.


Condition Intervention Phase
Graft Versus Host Disease
Drug: Rapamycin
Drug: Tacrolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Improvement of the rate of graft versus host disease (GVHD) from the accepted rate of 74%. [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival and disease free survival [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: February 2008
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Rapamycin
Rapamycin will be initiated 24 weeks post SCT, while the patient is on Tacrolimus. The initial dose of rapamycin is 12 mg of loading dose, followed by 4 mg daily. The dose will be adjusted to keep trough level at 3-12 ng/dl. Rapamycin will be continued at the therapeutic dose for 4 additional weeks after Tacrolimus is stopped. Rapamycin will then be tapered off over 2 weeks. The patients will be on 50% of steady state dose for one week and 25% of the steady state dose for the last week.
Other Names:
  • Sirolimus
  • Rapamune
Drug: Tacrolimus
Tacrolimus target level is 5-10 ng/dl. Tacrolimus taper will start at 26 weeks post SCT. Tacrolimus will be tapered off over 4-8 weeks. The rate of taper will be 25% every to weeks for patients on 4 mg or more tacrolimus daily. For the patients on 3 mg or less of tacrolimus, the dose will be reduced 1 mg every two weeks, and the last dose will be 1 mg every other day for two weeks.
Other Name: Prograf

  Eligibility

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

Inclusion Criteria:

  • Age ≥18 years
  • Received an allogeneic MSD or MUD PBSCT
  • 24 weeks post SCT
  • Currently on Tacrolimus for GVHD prophylaxis
  • Deemed eligible for tapering off of Tacrolimus by primary BMT physician

Exclusion Criteria:

  • Relapsed Disease
  • Ongoing GVHD
  • Patients whose immunosuppression is being stopped early to treat or prevent relapse
  • Patients with pure red cell aplasia due to ABO mismatched donor
  • Ongoing thrombotic microangiopathy
  • Allergy to rapamycin
  • Women of childbearing potential must have a negative serum pregnancy test performed prior to the start of treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00623012

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Stuart Seropian, M.D. Yale University
  More Information

No publications provided

Responsible Party: Stuart Seropian, Associate Professor, Yale University
ClinicalTrials.gov Identifier: NCT00623012     History of Changes
Other Study ID Numbers: 0702002350
Study First Received: February 13, 2008
Last Updated: July 15, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Sirolimus
Everolimus
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 23, 2014