This study is designed to test the combination of Plerixafor with G-CSF for chemosensitization in patients with relapsed or refractory AML.
In this study, we are seeking to target the leukemia microenvironment to overcome disease resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic chemotherapy. In this study, we seek to maximize blockage of the SDF-1/CXCR4 axis through the following: 1. Addition of G-CSF, which down regulates SDF-1 expression and acts synergistically with plerixafor in stem cell mobilization 2. Intravenous instead of subcutaneous dosing of plerixafor to improve kinetics of administration. 3. Dose escalation of plerixafor and twice daily dosing to maintain maximum CXCR4 blockade.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
MD Anderson Cancer Center
Houston, Texas, United States
Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC
Time frame: Completion of Phase I enrollment (17 months)
Phase II: Complete Response Rate (CR+CRi)
* Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1,000/mm3, platelet count \> 100,000/mm3. * Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia \<1,000/mm3 or thrombocytopenia \<100,000/mm3.
Time frame: 45 days
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Time frame: 30 days following end of treatment
Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
-Neutrophil recovery is defined as absolute neutrophil count (ANC) \>= 500/mm\^3
Time frame: Up to 62 days after treatment
Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
-Neutrophil recovery is defined as absolute neutrophil count \>= 1000/mm\^3
Time frame: Up to 62 days after treatment
Time to Hematologic Recovery as Measured by Time to Platelet Recovery
-Platelet recovery is defined as platelets \>= 50,000/mm\^3
Time frame: Up to 62 days after treatment
Time to Hematologic Recovery as Measured by Time to Platelet Recovery
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-Platelet recovery is defined as platelets \>= 100,000/mm3
Time frame: Up to 62 days after treatment
Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in White Blood Cells
Time frame: 6 hours after plerixafor
Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in AML Blast Count
Time frame: 6 hours after plerixafor
Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 1D9 Relative Mean Fluorescent Intensity
Time frame: 6 hours after plerixafor
Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 12G5 Relative Mean Fluorescent Intensity
Time frame: 6 hours after plerixafor
Time to Progression
Recurrence / morphologic relapse: Defined as reappearance of blasts in the blood or the finding of \> 5% blasts in the BM, not attributable to any other cause. New dysplastic changes are considered a relapse. If there are no blasts in the peripheral blood and 5-19% blasts in the BM, the BM biopsy and aspirate should be repeated in \> 1 week to confirm relapse.
Time frame: 2 years
Time to Treatment Failure
Time frame: 8 days
Overall Survival
Overall survival: Defined as the date of first dose of study drug to the date of death from any cause.
Time frame: Median follow-up was 34.6 months