Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

Study Overview
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Brief Summary
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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.

Official Title
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Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

Conditions
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Graft Versus Host Disease

Intervention / Treatment
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* Drug: Rapamycin
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Rapamycin<br>* 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.<br>* Other names: Rapamune;Drug: Tacrolimus<br>* 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.<br>* Other names: Prograf;|

What is the study measuring?
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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%. | Percentage of patients free from graft versus host disease | up to 8 weeks | 

Secondary Outcome Measures

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