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

• ClinicalTrials.gov Identifier: NCT02306291
• Recruitment Status: Completed
• First Posted: December 3, 2014
• Last Update Posted: May 17, 2019
• Sponsor: GlycoMimetics Incorporated
• Information provided by (Responsible Party): GlycoMimetics Incorporated

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia, Myeloid, Acute	Drug: GMI-1271; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine; Drug: Idarubicin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: December 2017
• Actual Study Completion Date: May 2018

Arms and Interventions

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 Name: 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 Name: 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 Name: Uproleselan; Drug: Cytarabine; induction chemotherapy; Drug: Idarubicin; induction chemotherapy

Outcome Measures

Primary Outcome Measures :

1. Safety assessed by frequency, severity and relatedness of adverse events [ Time Frame: up to 44 days ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States, 95817

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Michigan

University of Michigan, Ann Arbor

Ann Arbor, Michigan, United States, 48109

United States, New York

University of Rochester

Rochester, New York, United States, 14642

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Washington

University of Washington

Seattle, Washington, United States, 98109

Australia

Princess Alexandra Hospital

Brisbane, Australia

Ireland

University Hospital Galway

Galway, Ireland

Sponsors and Collaborators

GlycoMimetics Incorporated

Investigators

• Principal Investigator: Daniel DeAngelo, MD, PhD; Dana-Farber Cancer Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: GlycoMimetics Incorporated
• ClinicalTrials.gov Identifier: NCT02306291
• Other Study ID Numbers: GMI-1271-201
• First Posted: December 3, 2014
• Last Update Posted: May 17, 2019
• Last Verified: May 2019

Keywords provided by GlycoMimetics Incorporated:

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

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Cytarabine; Etoposide; Mitoxantrone; Idarubicin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Antibiotics, Antineoplastic