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
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: 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
Tacrolimus
Sirolimus
Everolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 16, 2014