Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients With AML Undergoing Allografting: Assessment of Feasibility and Efficacy

The study will be conducted as a single center Phase I/II study to evaluate the safety of administering PLERIXAFOR as part of a myeloablative preparative regimen (Institutional Protocol: FBT(400) - FLUDARABINE 50mg/m2/d x 4 days, BUSULFAN 3.2mg/kg/day x 4 days, TBI 400cGy in 2 fractions) for stem cell transplant recipients with Acute Myeloid Leukemia (AML) and to determine whether or not residual leukemic stem cells can be mobilized. Three patients will be enrolled into each of 4 sequential cohorts. Patients in the first cohort will receive 1 dose (240mcg/kg SC) of PLERIXAFOR ( MOZOBIL, formerly known as AMD3100) prior to administration of the first dose of FLUDARABINE and BUSULFAN It is planned to escalate the number of PLERIXAFOR doses in the subsequent cohorts to 2. 3. and 4 to be administered before the respective 2nd, 3rd, and 4th doses of chemotherapy. As primary endpoint the study will establish the toxicity of combined administration of PLERIXAFOR and the preparative regimen at each dose level. Secondary endpoints will include quantification of CXCR4 positive cells and candidates for leukemic disease propagating cells before and after administration of PLERIXAFOR. Mobilized cells will be examined for the ability to undergo apoptosis. Clinical parameters including SAE, OS and LFS are part of the evaluation.

The comparison of cell populations in peripheral blood before and after PLERIXAFOR may facilitate a better definition of minimal residual disease in patients deemed morphologically in a complete remission. The assessment after completion of the preparative regimen will provide a measurement of minimal residual disease prior to the transplant. The assessment of residual leukemic cells with respect to apoptosis will define their responsiveness to the administration of FLUDARABINE and BUSULFAN. The obtained information will facilitate development of a new platform to optimize preparation of patients for a transplant. Eg. Insufficient mobilization of leukemic cells may be addressed in future studies by combining mobilization strategies. Similarly, if cells are shown to be apoptosis resistant one may be able to include apoptosis inducing small molecules.