Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

Graft Versus Host Disease Clinical Trial

Official title:

Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00623012
• Other study ID #: 0702002350
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: February 13, 2008
• Last updated: July 15, 2013
• Start date: February 2008
• Est. completion date: August 2013

Study information

• Verified date: July 2013
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of the rate of graft versus host disease (GVHD) from the accepted rate of 74%.		Upon completion of study	No
Secondary	Overall survival and disease free survival		Upon completion of study	No