A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML
The interaction of leukemic blasts with the bone marrow microenvironment is postulated to be
an important mediator of chemoresistance in AML. Although a number of receptor / ligand
pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of
homing and retention of both normal and malignant hematopoietic cells in the marrow.
AMD3100 is a bicyclam molecule which reversibly blocks CXCR4 binding to SDF-1 and is being
developed clinically as a mobilization agent for hematopoietic stem cell transplantation.
Preclinical data from our group has demonstrated that in murine models, plerixafor can
disrupt the interaction of leukemic cells with the marrow microenvironment and sensitize
blasts to the effect of chemotherapy. Based on these data, we have initiated a phase I/II
study in patients with relapsed or refractory AML in which plerixafor is administered prior
to salvage chemotherapy.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the optimal dose and schedule of AMD3100 plus MEC in patients with relapsed or refractory AML
Length of Phase I
Geoffrey L. Uy, MD
Washington University School of Medicine
United States: Food and Drug Administration
07-0227 / 201011796
|Washington University||St. Louis, Missouri 63110|