Decitabine and Plerixafor in Elderly Acute Myeloid Leukemia (AML)

NCT01352650 | Completed Phase 1 DMC

• 1 other identifier: 1104011617
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

leukemia

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (6)

Cohort 1A

ACTIVE COMPARATOR

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; Drug: decitabine

Cohort 1B

ACTIVE COMPARATOR

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; Drug: decitabine

Cohort 2A

ACTIVE COMPARATOR

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; Drug: decitabine

Cohort 2B

ACTIVE COMPARATOR

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; Drug: decitabine

Cohort 3A

ACTIVE COMPARATOR

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; Drug: decitabine

Cohort 3B

ACTIVE COMPARATOR

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; Drug: decitabine

Interventions

plerixafor DRUG

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.

Also known as: MOZOBIL

Cohort 1A; Cohort 1B; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B

decitabine DRUG

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

Also known as: Dacogen

Cohort 1A; Cohort 1B; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (2)

• Roboz GJ, Ritchie EK, Dault Y, Lam L, Marshall DC, Cruz NM, Hsu HC, Hassane DC, Christos PJ, Ippoliti C, Scandura JM, Guzman ML. Phase I trial of plerixafor combined with decitabine in newly diagnosed older patients with acute myeloid leukemia. Haematologica. 2018 Aug;103(8):1308-1316. doi: 10.3324/haematol.2017.183418. Epub 2018 May 3.

  PMID: 29724902 DERIVED

• Allan JN, Roboz GJ, Askin G, Ritchie E, Scandura J, Christos P, Hassane DC, Guzman ML. CD25 expression and outcomes in older patients with acute myelogenous leukemia treated with plerixafor and decitabine. Leuk Lymphoma. 2018 Apr;59(4):821-828. doi: 10.1080/10428194.2017.1352089. Epub 2017 Jul 18.

  PMID: 28718760 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

plerixafor; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Gail Roboz, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: May 12, 2011
• Study Start: June 17, 2011
• Primary Completion: December 27, 2016
• Study Completion: December 27, 2016
• Last Updated: July 2, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)