A Phase I Trial Evaluating the Effects of Plerixafor (AMD3100) and G-CSF in Combination With Azacitidine (Vidaza) for the Treatment of MDS
The interaction of normal stem cells with the bone marrow microenvironment is mediated by a
number of factors. These interactions have been implicated in protecting malignant
hematopoietic cells from spontaneous apoptosis and genotoxic stresses such as chemotherapy.
Key elements are CXCR4, which is expressed on normal stem cells and leukemic blasts, and its
ligand, stromal derived factor 1 (SDF-1) expressed by bone marrow stromal cells and
osteoblasts. The CXCR4/SDF-1 axis is essential for homing, retention and mobilization of
stem cells from the bone marrow microenvironment. Plerixafor is a bicyclam small molecule
inhibitor of CXCR4 and has been extensively studied by our group and others as a potent stem
cell mobilization agent both in combination with G-CSF or alone (25, 62). Plerixafor is
currently being investigated in a phase I/II trial in combination with salvage chemotherapy
for relapsed AML in an attempt to sensitize leukemia stem cells to chemotherapy. The goal
of this study is to determine the optimal dose of plerixafor for the treatment of patients
with high-risk myelodysplastic syndrome (MDS) in combination with G-CSF and azacitidine. We
hypothesize that plerixafor in combination with G-CSF will detach MDS blasts from the bone
marrow microenvironment resulting in their increased proliferation and sensitivity to
azacitidine; thus, improving complete and partial response rates (CR/PR).
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the optimal dose and schedule of plerixafor + G-CSF and azacitidine in patients with MDS
The observation period for bone marrow aplasia as a DLT will be 42 days after the start of the second cycle of treatment or until the documentation of progression to leukemia. For all other toxicities, the DLT observation period will be 28 days from the start of treatment.
42 days after the start of the second cycle of treatment
Mark Schroeder, M.D.
Washington University School of Medicine
United States: Institutional Review Board
10-0150 / 201101810
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