Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

NCT ID: NCT00623012

Last Updated: 2017-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2013-08-31

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Sirolimus; Rapamune; Prograf

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stuart Seropian, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University School of Medicine

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

0702002350

Identifier Type: -

Identifier Source: org_study_id