Clinical trial NCT00146614: Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Blood Stem Cell Transplantation
Official title: Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Hematologic Malignancies
Keywords: Graft versus Host Disease
GVHD
Stem Cell Transplantation
Tacrolimus
Sirolimus
Methotrexate
allogeneic stem cell transplantation
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Beth Israel Deaconess Medical Center
name: Massachusetts General Hospital
First posted: 2005-09-07
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the incidence of Graft vs. Host Disease (GVHD) after non-myeloablative transplantation can be reduced by using a combination of three immune suppressive medication; sirolimus, tacrolimus and methotrexate.

Detailed description: * Patients will be admitted to the hospital and receive chemotherapy and stem cell transplant(SCT). The total duration of hospitalization for the procedure is approximately 8 days. Once admitted the patient will receive fludarabine daily for 4 days, busulfex once daily for 4 days. Two days after chemotherapy has ended, the patient will receive the infusion of donor cells.
* Just prior to the transplant and following the transplant, patients will receive sirolimus (orally), tacrolimus (orally) and low doses of methotrexate (chemotherapy). Methotrexate will be given on days 1,3 and 6 after transplant.
* Sirolimus will be tapered beginning week 9 after transplant if there is no evidence of GVHD and will be eliminated on week 26 if clinically feasible.
* Tacrolimus will be tapered beginning week 9 after transplant if there is no evidence of GVHD and will be eliminated on week 26 if clinically feasible.
* Patients will also receive medication to help prevent possible infection.
* After stem cell infusion, patients will be examined and have blood tests weekly for 1 month. At the 1 month visit, a bone marrow biopsy will performed looking for evidence of donor cells in the bone marrow. After the one month evaluation the patient will be examined every 2 weeks and a repeat bone marrow performed 3-4 months after transplant.

Eligibility criteria: Inclusion Criteria:

* Patients with hematologic malignancies who are at a high risk of complications after conventional transplantation.
* Donors (both related and unrelated) who are identical at 6 HLA loci.
* Age greater than 18
* ECOG Performance Status 0-2
* Life expectancy of greater than 100 days.

Exclusion Criteria:

* Pregnancy
* Evidence of HIV infection
* Heart failure uncontrolled by medications
* Total Bilirubin \> 2.0mg/dl due to hepatocellular dysfunction
* AST \> 90
* Serum creatinine \> 2.0
* Cholesterol \> 300 mg/dl

Primary outcomes:
measure: To assess the effect on the incidence and severity of GVHD by adding sirolimus, tacrolimus and methotrexate to GVHD prophylaxis.
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Isreal Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Edwin P. Alyea, MD
role: PRINCIPAL_INVESTIGATOR
References: