Decitabine and Plerixafor in Elderly Acute Myeloid Leukemia (AML)

Sponsor

Weill Medical College of Cornell University (Other)

Overall Status

Completed

CT.gov ID

NCT01352650

Collaborator

Genzyme, a Sanofi Company (Industry)

Enrollment

Location

Arms

66.4

Actual Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: plerixafor Drug: decitabine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

71 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 17, 2011

Actual Primary Completion Date :

Dec 27, 2016

Actual Study Completion Date :

Dec 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cohort 1A 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 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. Other Names: MOZOBIL Drug: decitabine 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 Other Names: Dacogen
Active Comparator: Cohort 1B 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 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. Other Names: MOZOBIL Drug: decitabine 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 Other Names: Dacogen
Active Comparator: Cohort 2A 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 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. Other Names: MOZOBIL Drug: decitabine 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 Other Names: Dacogen
Active Comparator: Cohort 2B 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 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. Other Names: MOZOBIL Drug: decitabine 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 Other Names: Dacogen
Active Comparator: Cohort 3A 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 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. Other Names: MOZOBIL Drug: decitabine 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 Other Names: Dacogen
Active Comparator: Cohort 3B 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 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. Other Names: MOZOBIL Drug: decitabine 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 Other Names: Dacogen

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.