Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

NCT00623012 | Terminated Phase 1 Results

• 1 other identifier: 0702002350
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall Survival

  up to 10 weeks

• Disease Free Survival

  up to 10 weeks

Study Arms (1)

1

EXPERIMENTAL

Drug: Rapamycin; Drug: Tacrolimus

Interventions

Rapamycin 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.

Also known as: Sirolimus, Rapamune

1

Tacrolimus 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.

Also known as: Prograf

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Received an allogeneic MSD or MUD PBSCT
• weeks post SCT
• Currently on Tacrolimus for GVHD prophylaxis
• Deemed eligible for tapering off of Tacrolimus by primary BMT physician

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Only 2 patients were enrolled. Early termination of trial, so patients were not followed long enough to see improvement.

Results Point of Contact

• Title: Dr. Stuart Seropian
• Organization: Yale University

Stuart.Seropian@yale.edu

203-737-2477

Study Officials

• Stuart Seropian, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2008
• First Posted: February 25, 2008
• Study Start: February 1, 2008
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: February 3, 2017
• Results First Posted: February 3, 2017

Record last verified: 2016-12

Locations

US (1)