Sirolimus With Tacrolimus for Graft-vs-Host Disease Prophylaxis After Un-Related Stem Cell Transplantation - Full Text View

Sponsored by:	Dana-Farber Cancer Institute
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00144677

Purpose

The purpose of this study is to evaluate the ability of sirolimus to prevent graft versus host disease (GVHD) in patients following stem cell transplant from an unrelated donor. This trial is designed to test the hypothesis that elimination of methotrexate in the unrelated donor group would lead to less transplant-related toxicity while still preserving the effective control of GVHD.

Condition	Intervention	Phase
Acute Myelogenous Leukemia Graft Versus Host Disease Acute Lymphoblastic Leukemia Chronic Myelogenous Leukemia Myelodysplastic Syndromes Non-Hodgkin's Lymphoma Hodgkin's Disease	Drug: sirolimus Drug: tacrolimus	Phase II

MedlinePlus related topics: Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Tacrolimus Sirolimus Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Open Label Phase II Trial of Sirolimus in Combination With Tacrolimus for Graft-vs-Host Disease Prophylaxis After HLA-Matched, Unrelated, Allogeneic Hematopoietic Stem Cell Transplantation

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To determine the feasibility of using a combination of sirolimus and tacrolimus without methotrexate for GVHD prophylaxis after stem cell transplantation.

Secondary Outcome Measures:

To compare the rates of grade II-IV and III-IV acute GVHD with historical control
to determine the incidence of 100 day mortality using this GVHD prophylaxis regimen
to determine the overall survival after one year of this patient population.

Estimated Enrollment:	30
Study Start Date:	November 2003
Study Completion Date:	June 2006
Primary Completion Date:	June 2006 (Final data collection date for primary outcome measure)

Detailed Description:

Therapy to prevent GVHD will consist of an infusion of tacrolimus intravenously and sirolimus orally once daily starting 3 days before stem cell infusion. This will take place in the hospital where the patient will remain for the duration of the transplant.
Sirolimus will continue for approximately 100 days at a stable dose, then it will be tapered slowly over the course of weeks to months to prevent a flare in GVHD.
Patients will be seen in the clinic weekly for the first 2 months after discharge from the hospital. If GVHD is present, tapering schedule will be slower and based on the patient's clinical condition.
Tacrolimus will also be given orally after the patient is discharged and will be tapered on the same schedule as sirolimus.
During the year following stem cell transplant, blood tests will be performed to evaluate the immune system and graft versus host disease.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Acute myelogenous leukemia(AML) in first or subsequent remission, in untreated first relapse or any treated relapse.
Acute lymphoblastic leukemia(ALL) in first or subsequent remission, in untreated first relapse or any treated relapse.
Chronic myelogenous leukemia in first or second chronic stable phase or in accelerated phase.
Myelodysplastic syndromes or myeloproliferative diseases
Non-Hodgkin's lymphoma or Hodgkin's disease in second or greater complete remission, in partial remission, or induction failure.
Chronic lymphocytic leukemia, Rai stage 2-4, which has progressed after initial therapy.
Matched unrelated donor.
Age 18-55 years at the time of stem cell transplantation
ECOG performance status 0-2
Life expectancy of 100 days without stem cell transplantation
Total bilirubin < 2.0 mg/dl
AST < 90 IU
Serum creatinine < 2.0 mg/dl
Ejection fraction > 40% by echocardiogram or gated nuclear medicine study.

Exclusion Criteria:

Uncontrolled infection
Forced vital capacity or DLCO < 50% predicted for age
Uncontrolled hypertension
Prior hematopoietic stem cell transplant
Evidence of HIV infection or active Hepatitis B or C infection
Cholesterol > 300 mg/dl
Relapsed aggressive Burkitt's or Burkitt's-like lymphoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00144677

Locations

United States, Massachusetts
Dana-Farber Cancer Center
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

Investigators

Principal Investigator:

Corey Cutler, MD, MPH

Dana-Farber Cancer Institute

More Information

Study ID Numbers:	03-290
Study First Received:	September 1, 2005
Last Updated:	December 20, 2007
ClinicalTrials.gov Identifier:	NCT00144677
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

Graft versus Host Disease
GVHD
sirolimus
tacrolimus
Stem cell transplant

Study placed in the following topic categories:

Sirolimus
Leukemia, Lymphoid
Hodgkin's disease
Precancerous Conditions
Chronic myelogenous leukemia
Clotrimazole
Graft versus host disease
Miconazole
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Hodgkin Disease

Lymphoma
Acute myelocytic leukemia
Myelodysplastic syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Tioconazole
Acute myelogenous leukemia
Myeloproliferative Disorders
Leukemia, Myeloid
Homologous wasting disease
Lymphatic Diseases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms by Histologic Type
Disease
Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic

Immunosuppressive Agents
Pharmacologic Actions
Anti-Bacterial Agents
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses
Antifungal Agents

ClinicalTrials.gov processed this record on January 16, 2009