Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant
Condition: Failure of Bone Marrow Graft
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II clinical trial will test the safety and the efficacy of post transplant
      administration of plerixafor in enhancing hematological recovery in humans. Patients who are
      appropriate candidates for myeloablative allogeneic stem cell transplantation from an
      HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for
      enrollment. The investigators plan to enroll a total of 50 patients for this study (30
      patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients with
      umbilical cord blood transplant). During phase I study, a small number of patients (3-6
      patients from each group) will be enrolled to determine the safety of post transplant
      administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg
      subcutaneously every other day beginning at day +2 after transplant until day +21 or
      engraftment. Limiting toxicities are defined as primary or secondary graft failure,
      plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are
      met from the investigators phase I study, the investigators will proceed with phase II study
      to determine the efficacy of post transplant administration of plerixafor in enhancing
      haematological recovery. The experimental aspect of this study is the use of plerixafor and
      all other aspects of care will be in line with the standard of care. Both Phase I and Phase
      II patients will be combined for efficacy analysis, and data collected from this study will
      be compared with the investigators historical control. The results from this study will set
      the stage and provide the justification for a larger phase 3 trial.
    

Detailed description: 
      Recruitment to this trial will be stratified by donor type as HLA (human leukocyte antigen)
      matched sibling, matched unrelated donor or umbilical cord blood. Patients will be
      conditioned with a myeloablative regimen such as, but not limited to, total body irradiation
      and cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of
      8/8 or 7/8 HLA-identical family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched
      unrelated donors, or dual umbilical cord blood grafts with at least 4 of 6 HLA matching at
      HLA A and B (low resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose
      will be 5 X 10(6)/kg recipient ideal body weight. For HLA matched sibling or matched
      unrelated donor (MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+
      cells/kg. For cord blood transplants, each unit will contain a minimum total nucleated cell
      count of of 1.5 X 10(7)/kg. Post-transplant GVHD (graft versus host disease) prophylaxis will
      be given per institutional standard.
    

Intervention name(s): Plerixafor
Intervention type(s): Drug
Intervention description(s): Matched sibling or Dual Cord donor subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Other intervention name(s): AMD3100; Mozobil
Intervention MeSH terms: Plerixafor
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Plerixafor and Allogeneic Myeloablative Stem Cell Transplant