Feasibility and Efficiency Study of Leukemic Cell Mobilization With Plerixafor Injection
Condition: Acute Myeloid Leukemia
Study type: Observational

Summary: 
      The study will be conducted as a single center Phase I/II study to evaluate the safety of
      administering Plerixafor administered as part of a myeloablative preparative regimen
      (Institutional Protocol:Fludarabine 50mg/m2/da x 4 days, Busulfan 3.2mg/kg/day x 4 days, TBI
      400cGy in divided fractions) for stem cell transplant recipients with 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 of
      Plerixafor (240mcg/kg sc) prior to administration of the first dose of Fludarabine and
      Busulfan. If tolerated 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
      dose of chemotherapy.
    

Detailed description: 
      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.
    

Intervention name(s): Plerixafor (mozobil)
Intervention type(s): Drug
Intervention description(s): Cohort 1: Administration of PLERIXAFOR (240mcg/kg sc) before the first dose of FLUDARABINE and BUSULFAN Cohort 2: Administration of PLERIXAFOR (240mcg/kg sc) before the first and second dose of FLUDARABINE and BUSULFAN.
Cohort 3: Administration of PLERIXAFOR (240mcg/kg sc) before the first, second, and third dose of FLUARABINE and BUSULFAN Cohort 4: Administration of PLERIXAFOR (240mcg/kg sc) before all four doses of FLUDARABINE and BUSULFAN
Other intervention name(s): Mozobil
Intervention MeSH terms: Plerixafor
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study will be performed on patients undergoing myeloablative allogeneic stem cell
        transplants (PBSC or BM) from related or unrelated donors for the treatment of patients
        with AML in remission.
      
Keywords: Plerixafor injection