Decitabine and Plerixafor in Elderly Acute Myeloid Leukemia (AML)

Phase 1

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: plerixafor; Drug: decitabine

• Registration Number: NCT01352650
• Lead Sponsor: Weill Medical College of Cornell University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-04-18
• Study First Submitted QC: 2011-05-11
• Study First Posted: 2011-05-12
• Study Start: 2011-06-17
• Primary Completion: 2016-12-27
• Study Completion: 2016-12-27
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-28
• Last Update Posted: 2018-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 3A	plerixafor	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
Cohort 3A	decitabine	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
Cohort 3B	plerixafor	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
Cohort 1A	plerixafor	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
Cohort 1A	decitabine	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
Cohort 1B	plerixafor	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
Cohort 1B	decitabine	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
Cohort 2A	plerixafor	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
Cohort 2A	decitabine	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
Cohort 2B	plerixafor	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
Cohort 2B	decitabine	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
Cohort 3B	decitabine	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

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States