Study to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in AML

NCT02306291 | Completed Phase 1 DMC

• 1 other identifier: GMI-1271-201
• Study Type: interventional
• Target: 91
• Locations: 3 countries
• Sites: 8

Brief Summary

This study will evaluate GMI-1271, a specific E-selectin antagonist, in acute myeloid leukemia in combination with standard agents used to treat this disease.

Conditions

Leukemia, Myeloid, Acute

Keywords

AML; Acute myeloid leukemia; E-selectin; relapse refractory; elderly newly diagnosed; induction

Outcome Measures

Primary Outcomes (1)

• Safety assessed by frequency, severity and relatedness of adverse events

  up to 44 days

Secondary Outcomes (6)

• Time versus plasma concentration profile of GMI-1271

  up to 11 days

• Overall response rate

  up to 12 months

• Time to response

  up to 12 months

• Duration of response

  up to 12 months

• Event-free survival

  up to 12 months

Study Arms (3)

Arm A (Phase I)

EXPERIMENTAL

GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older

Drug: GMI-1271; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Arm B (Phase II Arm A)

EXPERIMENTAL

GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older

Drug: GMI-1271; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Arm C (Phase II Arm B)

EXPERIMENTAL

GMI-1271 in combination with cytarabine and idarubicin (7+3 regimen) in newly diagnosed subjects 60 years and older

Drug: GMI-1271; Drug: Cytarabine; Drug: Idarubicin

Interventions

GMI-1271 DRUG

E-selectin antagonist

Also known as: Uproleselan

Arm A (Phase I); Arm B (Phase II Arm A); Arm C (Phase II Arm B)

Mitoxantrone DRUG

induction chemotherapy

Arm A (Phase I); Arm B (Phase II Arm A)

Etoposide DRUG

induction chemotherapy

Arm A (Phase I); Arm B (Phase II Arm A)

Cytarabine DRUG

induction chemotherapy

Arm A (Phase I); Arm B (Phase II Arm A); Arm C (Phase II Arm B)

Idarubicin DRUG

induction chemotherapy

Arm C (Phase II Arm B)

Eligibility Criteria

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

You may qualify if:

• AML (including secondary AML) diagnosed as per WHO criteria
• For relapsed/refractory subjects only:
• Subjects age ≥ 18 years with relapsed or refractory AML after ≤ 2 prior induction regimens, at least one containing anthracyclines
• Medically eligible to receive MEC
• Absolute blast count (ABC) ≤ 40,000/mm
• For treatment-naïve subjects only:
• Subjects ≥ 60 years of age with newly diagnosed AML
• Medically eligible to receive "7+3" cytarabine/idarubicin
• ABC count ≤ 40,000/mm
• ECOG performance status 0-2
• Hemodynamically stable and adequate organ function

You may not qualify if:

• Acute promyelocytic leukemia
• Acute leukemia of ambiguous lineage (biphenotypic leukemia)
• Active signs or symptoms of CNS involvement by malignancy
• No prior G-CSF, GM-CSF or plerixafor within 14 days of study drug dosing
• Known history or evidence of active hepatitis A, B, or C or HIV
• Uncontrolled acute life threatening bacterial, viral or fungal infection
• Active graft versus host disease (GVHD) ≥ Grade 2 or extensive chronic GVHD requiring immunosuppressive therapy
• Hematopoietic stem cell transplantation ≤ 4 months of dosing
• Clinically significant cardiovascular disease

Sponsors & Collaborators

• GlycoMimetics Incorporated: lead

Study Sites (8)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan, Ann Arbor

Ann Arbor, Michigan, 48109, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Princess Alexandra Hospital

Brisbane, Australia

Location

University Hospital Galway

Galway, Ireland

Location

Related Publications (1)

• DeAngelo DJ, Jonas BA, Liesveld JL, Bixby DL, Advani AS, Marlton P, Magnani JL, Thackray HM, Feldman EJ, O'Dwyer ME, Becker PS. Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022 Feb 24;139(8):1135-1146. doi: 10.1182/blood.2021010721.

  PMID: 34543383 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

uproleselan; Mitoxantrone; Etoposide; Cytarabine; Idarubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides

Study Officials

• Daniel DeAngelo, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 3, 2014
• Study Start: March 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: May 1, 2018
• Last Updated: May 17, 2019

Record last verified: 2019-05

Locations

AU (1); US (6); IE (1)