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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00144677
Recruitment Status : Completed
First Posted : September 5, 2005
Last Update Posted : January 26, 2012
Information provided by (Responsible Party):
Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute

Brief Summary:
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 or disease Intervention/treatment 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 2

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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Study Start Date : November 2003
Actual Primary Completion Date : June 2006
Actual Study Completion Date : June 2006

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

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

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00144677

United States, Massachusetts
Dana-Farber Cancer Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Principal Investigator: Corey Cutler, MD, MPH Dana-Farber Cancer Institute

Responsible Party: Corey S. Cutler, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT00144677     History of Changes
Other Study ID Numbers: 03-290
First Posted: September 5, 2005    Key Record Dates
Last Update Posted: January 26, 2012
Last Verified: March 2009

Keywords provided by Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute:
Graft versus Host Disease
Stem cell transplant

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Graft vs Host Disease
Leukemia, Myeloid, Acute
Hodgkin Disease
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors