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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	91 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group 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
Study Start Date :	March 2015
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	December 2018

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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; Dose escalation
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; Dose expansion
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; Safety run-in then dose expansion

Outcome Measures

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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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	GlycoMimetics Incorporated
ClinicalTrials.gov Identifier:	NCT02306291 History of Changes
Other Study ID Numbers:	GMI-1271-201
First Posted:	December 3, 2014
Last Update Posted:	October 30, 2017
Last Verified:	October 2017

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