Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia

A Phase III Randomized, Double-Blind Trial to Evaluate the Efficacy of Uproleselan Administered With Chemotherapy Versus Chemotherapy Alone in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This study will evaluate the efficacy of uproleselan (GMI-1271), a specific E-selectin antagonist, in combination with chemotherapy to treat relapsed/refractory AML, compared to chemotherapy alone. The safety of uproleselan when given with chemotherapy will also be investigated in patients with relapsed/refractory AML

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Uproleselan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 388
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Perth
    • Nedlands, Perth, Australia, 6009
      • Sir Charles Gairdner Hospital
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Cancer Clinical Trials Centre (CCTC)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center
    • Edmonton, Alberta, Canada
      • University of Alberta Princess Margaret Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada
      • The Leukemia/BMT Program of BC Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E0V9
      • CancerCare Manitoba
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • Toronto, Ontario, Canada, M5G 2MG
      • University Health Network (UHN) - Princess Margaret Cancer Centre
• France
  • Angers, France, 49933
    • Centre Hospitalier Universitaire d'Angers
  • Bordeaux, France, 33604
    • Centre Hospitalier Universitaire de Bordeaux
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire Grenoble Alpes
  • Marseille, France, 13273
    • Unité d'Evaluation Thérapeutique en Onco-Hématologie (ETHO)
  • Paris, France, 75010
    • Saint-Louis Hospital
  • Pierre-Bénite, France, 75010
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
• Ireland
  • Galway, Ireland, H91 TK33
    • Galway University Hospital
• Italy
  • Bologna, Italy, 40138
    • Institute of Hematology and Medical Oncology "L. and A. Seragnoli"
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
  • Ravenna, Italy, 48121
    • Hospital of Ravenna
  • Roma, Italy, 00133
    • Fondazione Policlinico Tor Vergata, U.O.C. Ematologia
  • Rome, Italy, 00168
    • Università Cattolica del Sacro Cuore (UNICATT)
  • Treviso, Italy, 31100
    • Ca' Foncello Hospital
  • FG
    • San Giovanni Rotondo, FG, Italy
      • IRCCS Casa Sollievo della Sofferenza Hospital
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Utrecht, Netherlands, 3584
    • University Medical Centre Utrecht
• Spain
  • Cáceres, Spain, 10003
    • Hospital San Pedro De Alcantra
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28033
    • Hospital MDACC
  • Málaga, Spain, 29010
    • Hospital Virgen de la Victoria, Málaga
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Santander, Spain, 39008
    • University Hospital of Hospital Marqués de Valdecilla
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XN
    • Cardiff University School of Medicine
  • England
    • Oxford, England, United Kingdom, OX3 7LJ
      • Radcliffe Hospitals and University of Oxford
• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moore Cancer Center
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles - UCLA
    • Orange, California, United States, 92868
      • University of California Irvine
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital - Medical Tower
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Hawthorne, New York, United States, 10532
      • Hudson Valley Cancer Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia University Herbert Irving Comprehensive Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System (DUHS)
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospital Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center and James Cancer Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt-Ingram Cancer Center Clinical Trials Office
  • Texas
    • Dallas, Texas, United States, 75246
      • Charles A. Sammons Cancer Center at Dallas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute, University of Utah
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years and ≤75 years in age
• Patients with relapsed or refractory AML
• No more than one prior stem cell transplant
• Has not received the chemotherapy regimen to be used for induction on this trial
• Is considered medically eligible to receive the chemotherapy regimen to be used for induction on this trial

Exclusion Criteria:

• Patients with acute promyelocytic leukemia, acute leukemia of ambiguous lineage (biphenotypic leukemia), chronic myeloid leukemia with myeloid blast crisis, or secondary refractory AML.
• Active signs or symptoms of CNS involvement by malignancy.
• Stem cell transplantation ≤4 months prior to dosing.
• Any immunotherapy or radiotherapy therapy within 28 days of dosing; any other experimental therapy or chemotherapy within 14 days of dosing.
• Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing.
• Inadequate organ function.
• Abnormal liver function.
• Known active infection with hepatitis A, B, or C, or human immunodeficiency virus.
• Moderate kidney dysfunction (glomerular filtration rate <45 mL/min).
• Uncontrolled acute life-threatening bacterial, viral, or fungal infection.
• Clinically significant cardiovascular disease.
• Major surgery within 4 weeks of dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Uproleselan (GMI-1271); Uproleselan in combination with mitoxantrone, etoposide and cytarabine (MEC) or fludarabine, cytarabine and idarubicin (FAI)	Drug: Uproleselan; A rationally designed E-selectin antagonist used to inhibit binding of cells to E-selectin
Placebo Comparator: Placebo (Saline, 0.9% Sodium Chloride); Placebo in combination with mitoxantrone, etoposide and cytarabine (MEC) or fludarabine, cytarabine and idarubicin (FAI)	Drug: Placebo; Saline, 0.9% Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from the date of randomization into the study to the date of death.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of severe oral mucositis	Incidence of severe oral mucositis experienced in patients after treatment.	up to 60 days
Overall response rate	Proportion of subjects who achieve a complete remission [CR] or CR with partial recovery [CRh] of blood counts	Up to 60 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Frequency, severity, and relatedness of adverse events.	up to 5 months
Pharmacokinetic exposure (amount of uproleselan in the blood)	The amount of uproleselan in the blood over time.	up to 6 days
Event-free survival	Time from date of randomization into the study to the date of treatment failure, relapse, or death from any cause; whichever occurs first.	5 years
Duration of remission	Time from date of first documented remission to date of relapse or death from any cause, whichever occurs first.	5 years
Event-free survival	Landmark analysis: Time from date of randomization into the study to the date of relapse or death from any cause; whichever occurs first.	1 year
Overall survival	Landmark analysis: Time from the date of randomization into the study to the date of death.	2 years
Overall survival	Landmark analysis: Time from the date of randomization into the study to the date of death.	3 years
Overall survival	Landmark analysis: Time from the date of randomization into the study to the date of death.	4 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: AML; acute myeloid leukemia; Relapsed AML; Refractory AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: GMI-1271-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No