Trial Information

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.