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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00144677
First received: September 1, 2005
Last updated: January 24, 2012
Last verified: March 2009
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided

Responsible Party: Corey S. Cutler, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00144677     History of Changes
Other Study ID Numbers: 03-290
Study First Received: September 1, 2005
Last Updated: January 24, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
Graft versus Host Disease
GVHD
sirolimus
tacrolimus
Stem cell transplant

Additional relevant MeSH terms:
Graft vs Host Disease
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Everolimus
Sirolimus
Tacrolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 22, 2014