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

A Phase I/II, Open-label Multicenter Trial to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: GMI-1271; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine; Drug: Idarubicin

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Princess Alexandra Hospital
• Ireland
  • Galway, Ireland
    • University Hospital Galway
• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan, Ann Arbor
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. AML (including secondary AML) diagnosed as per WHO criteria

2. 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

3. 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
4. ECOG performance status 0-2
5. Hemodynamically stable and adequate organ function

Exclusion criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Phase I); GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older	Drug: GMI-1271; E-selectin antagonist; Other Names: Uproleselan; Drug: Mitoxantrone; induction chemotherapy; Drug: Etoposide; induction chemotherapy; Drug: Cytarabine; induction chemotherapy
Experimental: Arm B (Phase II Arm A); GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older	Drug: GMI-1271; E-selectin antagonist; Other Names: Uproleselan; Drug: Mitoxantrone; induction chemotherapy; Drug: Etoposide; induction chemotherapy; Drug: Cytarabine; induction chemotherapy
Experimental: Arm C (Phase II Arm B); GMI-1271 in combination with cytarabine and idarubicin (7+3 regimen) in newly diagnosed subjects 60 years and older	Drug: GMI-1271; E-selectin antagonist; Other Names: Uproleselan; Drug: Cytarabine; induction chemotherapy; Drug: Idarubicin; induction chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety assessed by frequency, severity and relatedness of adverse events	up to 44 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time versus plasma concentration profile of GMI-1271	Plasma concentration of GMI-1271	up to 11 days
Overall response rate	Proportion of subjects who achieve a complete response (CR) or CR with incomplete blood count recovery (CRi) per local investigator assessment	up to 12 months
Time to response	Time from date of first dose to first documentation of response	up to 12 months
Duration of response	Time from date of first documented remission to the date of relapse or death from any cause, whichever occurs first	up to 12 months
Event-free survival	Time from date of first dose to the date of treatment failure, relapse, or death from any cause, whichever occurs first	up to 12 months
Overall survival	The probability of survival at 6 months (Phase 1) and 12 months (Phase 2), after the date of first dose of study drug	up to 12 months

Collaborators and Investigators

• Sponsor: GlycoMimetics Incorporated
• Investigators: Principal Investigator: Daniel DeAngelo, MD, PhD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: December 1, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: AML; Acute myeloid leukemia; E-selectin; relapse refractory; elderly newly diagnosed; induction
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Etoposide; Cytarabine; Idarubicin; Mitoxantrone
• Other Study ID Numbers: GMI-1271-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No