Busulfan-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies

A Phase I-II Study of Busulfan-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies

The purpose of this study is:

1. To establish the maximally tolerated dose (MTD) of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion.
2. To evaluate disease free and overall survival after this conditioning regimen in patients with advanced acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
3. To evaluate potential pharmacogenomic determinants of toxicity of this regimen.
4. To evaluate potential pharmacogenomic determinants of efficacy of this regimen.

Inclusion Criteria:

Phase I portion:

• Relapsed or refractory acute myelogenous or lymphoid leukemia.
• Chronic myelogenous leukemia in accelerated phase or blast-crisis.
• Recurrent or refractory malignant lymphoma or Hodgkin's disease
• Recurrent or refractory multiple myeloma.
• Chronic lymphocytic leukemia, relapsed or with poor prognostic features.
• Myeloproliferative disorder (polycythemia vera, myelofibrosis) with transformation
• Myelodysplastic syndromes with more than 5% blasts.

Phase II portion:

• AML with active disease or beyond CR2.
• MDS with more than 5% blasts.

Exclusion Criteria:

• Clinical progression. Such patients may be treated on other treatment protocols or at the investigator's discretion. Such patients will continue to be monitored for survival and, may be asked to continue to provide specimens for studies of minimal residual disease and immune reconstitution as other treatments are recommended.