Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and efficacy of performing unrelated stem cell transplants using intravenous busulfan and fludarabine as preparative therapy and tacrolimus plus methotrexate as the GVHD prophylaxis regimen. The goal is to demonstrate safety, aiming for a transplant related mortality rate (TRM) of < or equal to 40% at 100 days. A TRM of > or equal to 60% will be considered unacceptable. Another goal is to demonstrate efficacy by showing and overall survival of >40% at 1-year following transplant.

Official Title
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Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing Matched Unrelated Donor Stem Cell Transplantation

Conditions
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Chronic Myeloid Leukemia, Acute Myelogenous Leukemia, Myelodysplasia, Acute Lymphocytic Leukemia, Severe Aplastic Anemia, Non-Hodgkin's Lymphoma, Lymphoproliferative Disease, Multiple Myeloma, Advanced Myeloproliferative Disease

Intervention / Treatment
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* Drug: Busulfan/Fludarabine phosphate/Tacrolimus/Methotrexate/G-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No fully or single-antigen mismatched sibling donor is available to donate stem cells. Age >15 and <61 ECOG PS < or equal to 2 Adequate renal function with serum creatinine <2.0 mg/dl Pulmonary diffusing capacity >40% of predicted Cardiac ejection fraction >40% as measured by radionuclide wall motion study or echocardiography No active liver disease. Total bilirubin must be < or equal to 2.0 mg/dl. Alkaline phosphatase and AST must be less than three times the upper limit of normal. Patients with hepatitis C and active hepatitis B are eligible only if a liver biopsy is performed and there is < or equal to grade 2 inflammation. Patients wtih a history of HBV infection should be tested for HBeAg, antiHBe and HBV DNA (quantitative). Patients with active HBV viral replication should receive anti-viral therapy. Negative serology for the human immunodeficiency virus (HIV) Available HLA-matched donor (see HLA compatibility requirements below) Signed informed consent from the recipient Exclusion Criteria: Ongoing active infection Pregnancy and/or nursing Active, uncontrolled CNS leukemia Opinion of BMT Committee that autologous or mini-allogeneic transplant would be the preferable form of treatment Receipt of any chemotherapy within 3 weeks of study entry except for hydroxyurea or imatinib mesylate. Use of interferon within 3 months of starting therapy.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 61 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: Busulfan/Fludarabine phosphate/Tacrolimus/Methotrexate/G-CSF|Day Preparative Regimen for GVHD Prophylaxis 7 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV 6 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV 5 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV 4 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV 3 Fludarabine 30 mg/m(2)IV 2 REST Tacrolimus 0.01 mg/kg CIVI 1 REST 0 Unrelated Stem Cell/Bone Marrow Infusion 1 Methotrexate 5mg/m(2)IV 3 Methotrexate 5mg/m(2)IV 6 Methotrexate 5mg/m(2)IV 7 G-CSF 5mcg/kg SQ daily 11 Methotrexate 5mg/m(2)IV 90 Evaluate Response|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Matched Unrelated Donor, Stem Cell Transplantation, Busulfan, fludarabine, Hematopoietic Disorder