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

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

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.

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.