Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00623012
Recruitment Status : Terminated (Low accrual)
First Posted : February 25, 2008
Results First Posted : February 3, 2017
Last Update Posted : February 3, 2017
Information provided by (Responsible Party):
Yale University

Brief Summary:

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 or disease Intervention/treatment Phase
Graft Versus Host Disease Drug: Rapamycin Drug: Tacrolimus Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Rapamycin for Prevention of Chronic Graft-Versus-Host Disease
Study Start Date : February 2008
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Improvement of the Rate of Graft Versus Host Disease (GVHD) From the Accepted Rate of 74%. [ Time Frame: up to 8 weeks ]
    Percentage of patients free from graft versus host disease

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: up to 10 weeks ]
    achieved overall survival in regard to leukemia

  2. Disease Free Survival [ Time Frame: up to 10 weeks ]
    achieved disease free in regard to leukemia

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00623012

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

Responsible Party: Yale University Identifier: NCT00623012     History of Changes
Other Study ID Numbers: 0702002350
First Posted: February 25, 2008    Key Record Dates
Results First Posted: February 3, 2017
Last Update Posted: February 3, 2017
Last Verified: December 2016

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents