Clinical trial NCT00144703: Sirolimus With Tacrolimus for Graft-vs-Host Disease Prophylaxis After Related Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematologic Malignancies
Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Hodgkin's Disease
Keywords: Graft versus host disease
GVHD
Stem cell transplantation
sirolimus
tacrolimus
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
First posted: 2005-09-05
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 a related donor.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the feasibility of using sirolimus and tacrolimus without methotrexate for GVHD prophylaxis after stem cell transplantation.
Secondary outcomes:
measure: To compare the rates of grade II-IV and III-IV acute GVHD with historical controls
measure: to determine the incidence of 100 day mortality after stem cell transplant using this regimen
measure: to determine the overall survival at 1 year after transplantation in this patient population.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Corey Cutler, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: