Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

December 9, 2016 updated by: Yale University

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School Of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: up to 10 weeks
achieved overall survival in regard to leukemia
up to 10 weeks
Disease Free Survival
Time Frame: up to 10 weeks
achieved disease free in regard to leukemia
up to 10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Investigators

  • Principal Investigator: Stuart Seropian, M.D., Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

February 13, 2008

First Submitted That Met QC Criteria

February 13, 2008

First Posted (Estimate)

February 25, 2008

Study Record Updates

Last Update Posted (Estimate)

February 3, 2017

Last Update Submitted That Met QC Criteria

December 9, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0702002350

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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