Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Advanced Myeloproliferative Disease, Chronic Myeloid Leukemia, Lymphoproliferative Disease, Multiple Myeloma, Myelodysplasia, Non-Hodgkin's Lymphoma, Severe Aplastic Anemia
Conditions
Keywords
Matched Unrelated Donor, Stem Cell Transplantation, Busulfan, fludarabine, Hematopoietic Disorder
Brief summary
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.
Interventions
DRUGBusulfan/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
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 61 Years
Healthy volunteers
No
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.
Countries
United States
Outcome results
None listed