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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03616470
• Other study ID #: GMI-1271-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 15, 2018
• Est. completion date: December 2024

Study information

• Verified date: July 2023
• Source: GlycoMimetics Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 388
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Uproleselan
A rationally designed E-selectin antagonist used to inhibit binding of cells to E-selectin
• Placebo
Saline, 0.9% Sodium Chloride

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Townsville Hospital	Douglas	Queensland
Australia	Cancer Clinical Trials Centre (CCTC)	Heidelberg	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Perth
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	University of Alberta Princess Margaret Hospital	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	University Health Network (UHN) - Princess Margaret Cancer Centre	Toronto	Ontario
Canada	The Leukemia/BMT Program of BC Vancouver General Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	Centre Hospitalier Universitaire d'Angers	Angers
France	Centre Hospitalier Universitaire de Bordeaux	Bordeaux
France	Centre Hospitalier Universitaire Grenoble Alpes	La Tronche
France	Unité d'Evaluation Thérapeutique en Onco-Hématologie (ETHO)	Marseille
France	Saint-Louis Hospital	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
Ireland	Galway University Hospital	Galway
Italy	Institute of Hematology and Medical Oncology "L. and A. Seràgnoli"	Bologna
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola
Italy	Hospital of Ravenna	Ravenna
Italy	Fondazione Policlinico Tor Vergata, U.O.C. Ematologia	Roma
Italy	Università Cattolica del Sacro Cuore (UNICATT)	Rome
Italy	IRCCS Casa Sollievo della Sofferenza Hospital	San Giovanni Rotondo	FG
Italy	Ca' Foncello Hospital	Treviso
Netherlands	VU University Medical Center	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	University Medical Centre Utrecht	Utrecht
Spain	Hospital San Pedro De Alcantra	Cáceres
Spain	Hospital MDACC	Madrid
Spain	Hospital Universitario Fundación Jiménez Diaz	Madrid
Spain	Hospital Virgen de la Victoria, Málaga	Málaga
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	University Hospital of Hospital Marqués de Valdecilla	Santander
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United Kingdom	Cardiff University School of Medicine	Cardiff
United Kingdom	Radcliffe Hospitals and University of Oxford	Oxford	England
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital - Medical Tower	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospital Cleveland Medical Center	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center and James Cancer Hospital	Columbus	Ohio
United States	Charles A. Sammons Cancer Center at Dallas	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Health System (DUHS)	Durham	North Carolina
United States	Hudson Valley Cancer Center	Hawthorne	New York
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UC San Diego Moore Cancer Center	La Jolla	California
United States	University of California, Los Angeles - UCLA	Los Angeles	California
United States	Vanderbilt-Ingram Cancer Center Clinical Trials Office	Nashville	Tennessee
United States	Columbia University Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of California Irvine	Orange	California
United States	Stanford Cancer Institute	Palo Alto	California
United States	University of Rochester Medical Center	Rochester	New York
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	The University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest Baptist Hospital	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlycoMimetics Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Ireland,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Duration of remission	Time from date of first documented remission to date of relapse or death from any cause, whichever occurs first.	5 years
Other	Adverse events	Frequency, severity, and relatedness of adverse events.	up to 5 months
Other	Pharmacokinetic exposure (amount of uproleselan in the blood)	The amount of uproleselan in the blood over time.	up to 6 days
Other	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
Other	Overall survival	Landmark analysis: Time from the date of randomization into the study to the date of death.	2 years
Other	Overall survival	Landmark analysis: Time from the date of randomization into the study to the date of death.	3 years
Other	Overall survival	Landmark analysis: Time from the date of randomization into the study to the date of death.	4 years
Primary	Overall survival	Time from the date of randomization into the study to the date of death.	5 years
Secondary	Rate of severe oral mucositis	Incidence of severe oral mucositis experienced in patients after treatment.	up to 60 days
Secondary	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