Acute Myeloid Leukemia
Conditions
Keywords
leukemia
Brief summary
The hypothesis of this proposal is that combining plerixafor, an inhibitor of stromal cell derived factor - 1α (SDF-1α), with decitabine, a DNA methyltransferase inhibitor, as induction and postremission therapy for older patients with Acute Myeloid Leukemia (AML) will improve treatment outcomes via mobilization of leukemia stem cells and alteration of the pharmacodynamics of decitabine. The protocol will establish the safety and feasibility of combining two different doses of plerixafor with a fixed dose and schedule of decitabine.
Interventions
DRUGplerixafor
Cohort 1 will receive plerixafor at a dose of 320 mcg/kg, cohort 2 will receive plerixafor at a dose of 540 mcg/kg and cohort 3 will receive plerixafor at a dose of 810 mcg/kg. Schedule A will receive plerixafor on the 2nd and 4th cycles and Schedule B will receive plerixafor on the 1st and 3rd cycles of treatment.
DRUGdecitabine
decitabine will be given to all cohorts/schedules at 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 for all cycles
Sponsors
Genzyme, a Sanofi Company
Weill Medical College of Cornell University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unequivocal pathologic diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO criteria) excluding: i) acute promyelocytic leukemia t(15;17)(q22;q12); PML-RARA; ii)acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNXT1; iii) acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11. * AML patients with an antecedent hematologic disorder or myelodysplastic syndrome (MDS)are eligible for treatment on this trial provided that they have not received prior treatment with decitabine or prior cytotoxic treatment for AML. * AML patients with therapy-related myeloid neoplasms (t-MN) are eligible if they have not received chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for \>6 months. * Age ≥ 60 years. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Prior treatment with decitabine * Prior treatment with plerixafor * Ongoing treatment for another malignancy. * Patients with good-risk molecular or cytogenetics features * Patient has a medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational drug treatment. * Patient has a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies. * Patient has an inability or unwillingness, in the opinion of the investigator, to comply with the protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| response to treatment | after every cycle (every month) - average subject will be on study for 4-6 months | blood and bone marrow testing will be done to determine response to treatment every month |
Countries
United States
Outcome results
None listed