Decitabine and Plerixafor in Elderly Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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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.

Official Title
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Induction Therapy With Decitabine and Plerixafor Priming for Patients ≥ 60 Years With Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: plerixafor
* Drug: decitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1A<br>Cycle 1: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 2: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 320 mcg/kg IV on days 1-5 Cycle 3: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 4: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 320 mcg/kg IV on days 1-5 | Drug: plerixafor<br>* 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.<br>* Other names: MOZOBIL;Drug: decitabine<br>* 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<br>* Other names: Dacogen;|
| Active Comparator: Cohort 1B<br>Cycle 1: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 320 mcg/kg IV on days 1-5 Cycle 2: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 3: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 320 mcg/kg IV on days 1-5 Cycle 4: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 | Drug: plerixafor<br>* 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.<br>* Other names: MOZOBIL;Drug: decitabine<br>* 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<br>* Other names: Dacogen;|
| Active Comparator: Cohort 2A<br>Cycle 1: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 2: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 540 mcg/kg IV on days 1-5 Cycle 3: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 4: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 540 mcg/kg IV on days 1-5 | Drug: plerixafor<br>* 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.<br>* Other names: MOZOBIL;Drug: decitabine<br>* 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<br>* Other names: Dacogen;|
| Active Comparator: Cohort 2B<br>Cycle 1: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 540 mcg/kg IV on days 1-5 Cycle 2 decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 3: decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 540 mcg/kg IV on days 1-5 Cycle 4 decitabine 20 mg/m2 IV daily for a 1-hour infusion on days 1-10 | Drug: plerixafor<br>* 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.<br>* Other names: MOZOBIL;Drug: decitabine<br>* 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<br>* Other names: Dacogen;|
| Active Comparator: Cohort 3A<br>Cycle 1: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 2: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 810 mcg/kg IV on days 1-5 Cycle 3: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 4: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 810 mcg/kg IV on days 1-5 | Drug: plerixafor<br>* 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.<br>* Other names: MOZOBIL;Drug: decitabine<br>* 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<br>* Other names: Dacogen;|
| Active Comparator: Cohort 3B<br>Cycle 1: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 810 mcg/kg IV on days 1-5 Cycle 2: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 Cycle 3: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 + plerixafor 810 mcg/kg IV on days 1-5 Cycle 4: decitabine 20mg/m2 IV daily for a 1-hour infusion on days 1-10 | Drug: plerixafor<br>* 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.<br>* Other names: MOZOBIL;Drug: decitabine<br>* 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<br>* Other names: Dacogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response to treatment | blood and bone marrow testing will be done to determine response to treatment every month | after every cycle (every month) - average subject will be on study for 4-6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leukemia