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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Open Label Phase II Trial of Sirolimus in Combination With Tacrolimus for Graft-vs-Host Disease Prophylaxis After Matched, Related Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00144703
• Other study ID #: 02-090
• Status: Completed
• Phase: Phase 2
• First received: September 1, 2005
• Last updated: January 24, 2012
• Start date: July 2002
• Est. completion date: November 2006

Study information

• Verified date: January 2009
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 a related donor.

Description:

• Therapy to prevent GVHD will consist of an infusion of tacrolimus intravenously and sirolimus orally once per day 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 9 weeks at at stable dose, then will be tapered by 1/3 on week 9 and 1/3 on week 17. It will be stopped on week 26 if there is no significant evidence of GVHD. These dose modifications will occur at home and patients will be seen weekly for the first 2 months after discharge.

• If GVHD is present, the tapering schedule wil be slower and based upon the patient's clinical condition.

• Tacrolimus will be given orally once the patient is discharged from the hospital and will be tapered at the same schedule as sirolimus. Blood levels of both tacrolimus and sirolimus will be monitored and the dose adjusted accordingly.

• During the year following stem cell transplant, blood work will be performed to evaluate the immune system and GVHD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: November 2006
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with hematologic malignancies who will undergo allogeneic HSCT from matched family-members.

• Age greater than 18

• ECOG performance status 0-2

• Total bilirubin < 2.0 mg/dl

• AST < 90 IU

• Serum creatinine < 2.0 mg/dl

Exclusion Criteria:

• Active, uncontrolled infection

• Ejection fraction < 45% by echocardiogram or MUGA scan

• Forced vital capacity < 60%

• Uncontrolled hypertension

• Second transplantation

• Evidence of HIV infection

• Cholesterol > 300 mg/dl

• Relapsed aggressive Burkitt's or Burkitt's-like lymphoma

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Graft vs Host Disease
• Hematologic Malignancies
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Myelogenous Leukemia
• Non-Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• Sirolimus

• Tacrolimus

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the feasibility of using sirolimus and tacrolimus without methotrexate for GVHD prophylaxis after stem cell transplantation.
Secondary	To compare the rates of grade II-IV and III-IV acute GVHD with historical controls
Secondary	to determine the incidence of 100 day mortality after stem cell transplant using this regimen
Secondary	to determine the overall survival at 1 year after transplantation in this patient population.