Tacrolimus and Sirolimus as Prophylaxis After Allogenic Non-myeloablative Peripheral Blood Stem Cell Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to extend the use of Tacrolimus and Sirolimus to determine how effective it is in preventing graft versus host disease (GVHD)in patients that have received non-myeloablative peripheral blood stem cell transplantation.

Detailed Description
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After the screening procedures confirm that the patient is eligible to participate in the research study, they will be admitted to the hospital to receive chemotherapy and stem cell transplantation (SCT). The duration of the hospitalization for the procedure is approximately 8 days. Patients will receive fludarabine once daily over 30 minutes intravenously for 4 days and busulfex once daily over 3 hours intravenously each day for the same 4 days. Just prior to the transplant and following the transplant the patient will receive sirolimus and tacrolimus to help prevent Graft versus Host Disease (GvHD). Both medications are taken orally. Patients will also take medications to help prevent possible infections (e.g. acyclovir). Filgrastim, a white blood cell growth factor, will be given daily in an injection under the skin, starting the day after the stem cell transplant and until the patients blood counts have recovered. After the stem cell infusion, the patient will be examined and have blood tests weekly for 1 month. At about the 1-month visit, a bone marrow biopsy and/or blood tests will be performed to determine the percentage of donor's cells in the blood or bone marrow. These tests will be repeated at 3-4 months after transplant. At 3-4 months after the transplant, patients will also have tests to reassess the response of your disease to transplant. This may involve a bone marrow biopsy, blood tests, and/or radiology studies depending upon the type of cancer. Follow-up will continue for the remainder of the patients life.

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

Conditions
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Graft Versus Host Disease, GVHD

Intervention / Treatment
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* Drug: tacrolimus
* Drug: sirolimus
* Drug: fludarabine
* Drug: busulfex


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 Availability of a related donor who is identical at 6 HLA loci Greater than 18 years of age Performance status 0-2 Life expectancy of > 100 days Exclusion Criteria: Pregnancy Evidence of HIV infection Heart failure uncontrolled medication Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction AST >90 Serum Creatinine >2.0 Cholesterol > 300mg/dl while adequately treated

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tacrolimus|Given orally just prior to and following stem cell transplant|
|Drug: sirolimus|Given orally just prior to and following stem cell transplant|
|Drug: fludarabine|Given once daily over 30 minutes for 4 days|
|Drug: busulfex|Given intravenously over 3 hours for 4 days|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade II-IV Acute GVHD (aGVHD) Developing by Day 100 Following Non-myeloablative PBSC Transplantation Using Tacrolimus and Sirolimus. | All participants received tacrolimus and sirolimus in this one arm study. There were no participants considered unevaluable for this measure (deceased prior to day 100). The total number of people who developed grade II-IV aGVHD before day 100 are reported here. | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥90 Percent Donor-derived Hematopoeisis Around 100 Days Post Transplantation | The percentage of participants with ≥90 percent donor-derived hematopoeisis was assessed around day +100 using peripheral blood chimerism. | 100 days | 
| Disease Response. | Disease response was assessed as 2 year progression-free survival. The median follow-up time was 1.84 years. The percentage of participants with who reached this timepoint with no disease progression are reported. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-myeloablative peripheral blood stem cell, PBSCT, tacrolimus, sirolimus