Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Blood Stem Cell Transplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation

Conditions
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Graft Versus Host Disease, Hematologic Malignancies

Intervention / Treatment
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* Drug: Sirolimus
* Drug: Tacrolimus
* Drug: Methotrexate
* Procedure: Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sirolimus|nan|
|Drug: Tacrolimus|nan|
|Drug: Methotrexate|nan|
|Procedure: Stem Cell Transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect on the incidence and severity of GVHD by adding sirolimus, tacrolimus and methotrexate to GVHD prophylaxis. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft versus Host Disease, GVHD, Stem Cell Transplantation, Tacrolimus, Sirolimus, Methotrexate, allogeneic stem cell transplantation