Trial Information

Ex Vivo Expansion of Mafosfamide Purged CD34+ Cells in Patients With Acute Leukemia

OBJECTIVES:

- Determine the feasibility of ex vivo expanded mafosfamide-purged CD34-positive cells
for autologous peripheral blood stem cell or bone marrow transplantation in patients
with acute leukemia.

- Determine the duration of aplasia associated with the use of ex vivo cytokine expanded
mafosfamide-purged cells in patients treated with this regimen.

- Determine, preliminarily, the event-free survival of patients treated with this
regimen.

OUTLINE: This is a pilot study.

- Mobilization and stem cell collection: Patients receive cyclophosphamide IV and
filgrastim (G-CSF) subcutaneously (SC) or IV once daily for 7-14 days followed by
leukapheresis to collect peripheral blood stem cells (PBSCs). Some patients may also
undergo bone marrow (BM) harvest if sufficient PBSCs are not collected. Patients with a
sufficient number of stem cells or BM (5 x 10^6 PBSC/kg or 3 x 10^8 BM cells/kg)
proceed to autologous PBSC transplantation (PBSCT) or BM transplantation (BMT).

- CD34-positive cell selection and mafosfamide purging: Collected PBSCs and/or BM are
treated in the laboratory to isolate CD34-positive cells. A minimum of 1 x 10^6
nucleated CD34-positive BM cells/kg or 2 x 10^6 nucleated CD34-positive PBSCs/kg must
be available after selection to proceed to mafosfamide-purging. The selected cells are
then treated in vitro with mafosfamide to purge remaining leukemic cells. One third of
the mafosfamide-purged cells are then cryopreserved for future use and 2/3 of the
mafosfamide-purged cells proceed to ex vivo expansion.

- Ex vivo expansion: The remaining CD34-positive mafosfamide-purged cells are treated in
vitro with stem cell factor, G-CSF, and recombinant human thrombopoietin and incubated
for 12-14 days.

- Myeloablative therapy: Patients receive busulfan on days -9 to -6 and cyclophosphamide
on days -5 to -2.

- PBSCT or BMT: Patients undergo autologous PBSCT or BMT using CD34-positive
mafosfamide-purged cryopreserved cells and ex vivo expanded CD34-positive
mafosfamide-purged cells on day 0 followed by G-CSF SC or IV once daily until blood
counts recover.

After completion of study treatment, patients are followed periodically for at least 5
years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.