Rapamycin for Prevention of Chronic Graft-Versus-Host Disease - Full Text View

Sponsors and Collaborators:	Yale University Wyeth
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00623012

Purpose

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.

Condition	Intervention	Phase
Graft Versus Host Disease	Drug: Rapamycin Drug: Tacrolimus	Phase I Phase II

Drug Information available for: Tacrolimus Sirolimus Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	Rapamycin for Prevention of Chronic Graft-Versus-Host Disease

Further study details as provided by Yale University:

Primary Outcome Measures:

Improvement of the rate of graft versus host disease (GVHD) from the accepted rate of 74%. [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival and disease free survival [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	February 2008
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	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. 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.

Arms

Assigned Interventions

1: Experimental

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623012

Contacts

Contact: Noelle Sowers, RN	203-785-2442	noelle.sowers@yale.edu
Contact: Donna LaCivita	203-737-2579	donna.lacivita@yale.edu

Locations

United States, Connecticut
Yale University School of Medicine	Recruiting
New Haven, Connecticut, United States, 06520

Sponsors and Collaborators

Yale University

Wyeth

Investigators

Principal Investigator:

Stuart Seropian, M.D.

Yale University

More Information

Responsible Party:	Yale University School of Medicine ( Stuart Seropian, M.D. Principal Investigator )
Study ID Numbers:	0702002350
Study First Received:	February 13, 2008
Last Updated:	December 5, 2008
ClinicalTrials.gov Identifier:	NCT00623012
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Sirolimus
Clotrimazole
Graft versus host disease
Miconazole

Tioconazole
Graft vs Host Disease
Tacrolimus
Homologous wasting disease

Additional relevant MeSH terms:

Anti-Bacterial Agents
Anti-Infective Agents
Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Antifungal Agents

Therapeutic Uses
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009