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

Sponsor

GlycoMimetics Incorporated (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03616470

Collaborator

(none)

388

Enrollment

Locations

Arms

61.5

Anticipated Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Uproleselan Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

388 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 15, 2018

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall survival [5 years]
Time from the date of randomization into the study to the date of death.

Secondary Outcome Measures

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

Other Outcome Measures

Event-free survival [2 years]
Time from date of randomization into the study to the date of treatment failure, relapse, or death from any cause; whichever occurs first.
Duration of remission [2 years]
Time from date of first documented remission to date of relapse or death from any cause, whichever occurs first.
Adverse events [up to 5 months]
Frequency, severity, and relatedness of adverse events.
Pharmacokinetic exposure (amount of uproleselan in the blood) [up to 6 days]
The amount of uproleselan in the blood over time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC San Diego Moore Cancer Center	La Jolla	California	United States	92093
2	University of California, Los Angeles - UCLA	Los Angeles	California	United States	90095
3	University of California Irvine	Orange	California	United States	92868
4	Stanford Cancer Institute	Palo Alto	California	United States	94304
5	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
6	Emory Winship Cancer Institute	Atlanta	Georgia	United States	30322
7	Northside Hospital - Medical Tower	Atlanta	Georgia	United States	30342
8	Rush University Medical Center	Chicago	Illinois	United States	60612
9	The University of Kansas Cancer Center	Westwood	Kansas	United States	66205
10	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
11	University of Michigan	Ann Arbor	Michigan	United States	48109
12	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
15	Hudson Valley Cancer Center	Hawthorne	New York	United States	10532
16	Columbia University Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
17	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
18	Weill Cornell Medical College	New York	New York	United States	10065
19	University of Rochester Medical Center	Rochester	New York	United States	14642
20	Duke University Health System (DUHS)	Durham	North Carolina	United States	27710
21	Wake Forest Baptist Hospital	Winston-Salem	North Carolina	United States	27157
22	University Hospital Cleveland Medical Center	Cleveland	Ohio	United States	44106
23	Cleveland Clinic	Cleveland	Ohio	United States	44195
24	The Ohio State University Wexner Medical Center and James Cancer Hospital	Columbus	Ohio	United States	43210
25	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
26	Vanderbilt-Ingram Cancer Center Clinical Trials Office	Nashville	Tennessee	United States	37203
27	Charles A. Sammons Cancer Center at Dallas	Dallas	Texas	United States	75246
28	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
29	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah	United States	84112
30	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
31	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
32	Sir Charles Gairdner Hospital	Nedlands	Perth	Australia	6009
33	Townsville Hospital	Douglas	Queensland	Australia	4814
34	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
35	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
36	Cancer Clinical Trials Centre (CCTC)	Heidelberg	Victoria	Australia	3084
37	Tom Baker Cancer Center	Calgary	Alberta	Canada	T2N 4N2
38	University of Alberta Princess Margaret Hospital	Edmonton	Alberta	Canada
39	The Leukemia/BMT Program of BC Vancouver General Hospital	Vancouver	British Columbia	Canada
40	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E0V9
41	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
42	University Health Network (UHN) - Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2MG
43	Centre Hospitalier Universitaire d'Angers	Angers		France	49933
44	Centre Hospitalier Universitaire de Bordeaux	Bordeaux		France	33604
45	Centre Hospitalier Universitaire Grenoble Alpes	La Tronche		France	38700
46	Unité d'Evaluation Thérapeutique en Onco-Hématologie (ETHO)	Marseille		France	13273
47	Saint-Louis Hospital	Paris		France	75010
48	Centre Hospitalier Lyon Sud	Pierre-Bénite		France	75010
49	Centre Hospitalier Universitaire de Poitiers	Poitiers		France	86021
50	Galway University Hospital	Galway		Ireland	H91 TK33
51	IRCCS Casa Sollievo della Sofferenza Hospital	San Giovanni Rotondo	FG	Italy
52	Institute of Hematology and Medical Oncology "L. and A. Seràgnoli"	Bologna		Italy	40138
53	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola		Italy	47014
54	Hospital of Ravenna	Ravenna		Italy	48121
55	Fondazione Policlinico Tor Vergata, U.O.C. Ematologia	Roma		Italy	00133
56	Università Cattolica del Sacro Cuore (UNICATT)	Rome		Italy	00168
57	Ca' Foncello Hospital	Treviso		Italy	31100
58	Amsterdam UMC (former VUMC)	Amsterdam		Netherlands	1081 HZ
59	University Medical Center Groningen	Groningen		Netherlands	9713 GZ
60	University Medical Centre Utrecht	Utrecht		Netherlands	3584
61	Hospital San Pedro De Alcantra	Cáceres		Spain	10003
62	Hospital MDACC	Madrid		Spain	28033
63	Hospital Universitario Fundación Jiménez Diaz	Madrid		Spain	28040
64	Hospital Virgen de la Victoria, Málaga	Málaga		Spain	29010
65	Clínica Universidad de Navarra	Pamplona		Spain	31008
66	Hospital Universitario de Salamanca	Salamanca		Spain	37007
67	University Hospital of Hospital Marqués de Valdecilla	Santander		Spain	39008
68	Hospital Universitari i Politècnic La Fe	Valencia		Spain	46026
69	Radcliffe Hospitals and University of Oxford	Oxford	England	United Kingdom	OX3 7LJ
70	Cardiff University School of Medicine	Cardiff		United Kingdom	CF14 4XN