ENHANCE: Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04313881

Collaborator

(none)

520

Enrollment

166

Locations

Arms

71.7

Anticipated Duration (Months)

3.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of magrolimab in combination with azacitidine compared to that of azacitidine plus placebo in previously untreated participants with intermediate/high/very high risk myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R) as measured by complete remission (CR) and overall survival (OS).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Magrolimab Drug: Azacitidine Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

520 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome

Actual Study Start Date :

Sep 9, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Magrolimab + Azacitidine Participants will receive the following magrolimab and azacitidine dosing regimens: Magrolimab: Magrolimab Priming Dose: 1 mg/kg on Days 1 and 4 15 mg/kg on Day 8 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50) Magrolimab Maintenance Dose: 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter Azacitidine: 75 mg/m^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle	Drug: Magrolimab Administered intravenously Other Names: Hu5F9-G4 GS-4721 Drug: Azacitidine Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling
Placebo Comparator: Control Arm (Placebo + Azacitidine) Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitadine: Placebo Priming Dose: 1 mg/kg on Days 1 and 4 15 mg/kg on Day 8 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50) Placebo Maintenance Dose: 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter Azacitidine: 75 mg/m^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle	Drug: Azacitidine Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling Drug: Placebo Placebo to match magrolimab administered intravenously

Arm

Intervention/Treatment

Experimental: Magrolimab + Azacitidine

Participants will receive the following magrolimab and azacitidine dosing regimens: Magrolimab: Magrolimab Priming Dose: 1 mg/kg on Days 1 and 4 15 mg/kg on Day 8 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50) Magrolimab Maintenance Dose: 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter Azacitidine: 75 mg/m^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle

Drug: Magrolimab

Administered intravenously

Other Names:

Hu5F9-G4

GS-4721

Drug: Azacitidine

Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling

Placebo Comparator: Control Arm (Placebo + Azacitidine)

Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitadine: Placebo Priming Dose: 1 mg/kg on Days 1 and 4 15 mg/kg on Day 8 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50) Placebo Maintenance Dose: 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter Azacitidine: 75 mg/m^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle

Drug: Azacitidine

Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling

Drug: Placebo

Placebo to match magrolimab administered intravenously

Outcome Measures

Primary Outcome Measures

Proportion of Participants with Complete Remission (CR) [Up to 24 months]
The CR rate is the proportion of participants who reach morphologic CR based on Investigator-assessed International Working Group (IWG) 2006 Myelodysplastic Syndrome (MDS) criteria (Cheson 2006) prior to initiation of any new MDS therapy including stem cell therapy (SCT).
Overall Survival (OS) [Up to 5 years]
OS is defined as the length measured from randomization to the date of death from any cause.

Secondary Outcome Measures

Duration of CR [Up to 5 years]
The duration of CR is measured from the time measurement criteria are first met for CR to the first date of relapse or death, whichever occurs earlier.
Objective Response Rate (ORR) [Up to 5 years]
ORR is the proportion of participants who reach objective response including CR, PR, marrow CR, or hematologic improvement per IWG 2006 MDS criteria prior to initiation of any new anticancer therapy for MDS, including SCT.
Duration of Response (DOR) [Up to 5 years]
DOR is measured from the time measurement criteria are first met for objective response to the first date of relapse, disease progression or death, whichever occurs earlier.
Red Blood Cell (RBC) Transfusion Independence Rate [Up to 5 years]
The RBC transfusion independence rate is the proportion of participants who have a 56-day or longer period with no RBC transfusions.
Progression Free Survival (PFS) [Up to 5 years]
PFS is defined as the time from randomization to the date of documented disease progression (including treatment failure by IWG criteria or relapse after PR/CR), or death from any cause, whichever occurs first.
Event Free Survival (EFS) [Up to 5 years]
The length of EFS is defined as the time from randomization to transformation to acute myeloid leukemia (AML) or death from any cause, whichever occurs first.
Minimal Residual Disease (MRD)-negative Response Rate [Up to 5 years]
The MRD-negative response rate is defined as the proportion of participants who achieve a morphologic CR or marrow CR based on Investigator-assessed IWG criteria {Cheson 2006} and reach MRD-negative disease status prior to initiation of any new anticancer therapy for MDS, including SCT.
Time to Transformation to Acute Myeloid Leukemia (AML) [Up to 5 years]
Time to transformation to AML is defined as the time from randomization to the collection date of bone marrow sample leading to documented AML diagnosis.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events [Up to 5 years]
Serum Concentration of Magrolimab [Up to 12 hours before administration of any treatment at Days 1 and 8 of Cycle1; at Day 1 of Cycles 2, 3, 5, 7, 10, and 13, and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days]
Anti-magrolimab Antibody Positivity Occurrence Rate [Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days]
Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate [Up to 5 years]
The FACT-Anemia response rate is defined as the proportion of participants who showed clinically meaningful improvement in health-related quality of life (HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new anticancer therapy for MDS, including SCT. The FACT-Anemia instrument consists of 5 subscales, including physical well-being, emotional well-being, functional well-being, social well-being, and anemia symptoms. Each subscale measures items on a 5-point Likert scale from 0 to 4, where 0 = not at all and 4 = very much.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
Adequate performance status and hematological, liver, and kidney function

Key Exclusion Criteria:

Immediate eligibility for allogenic stem cell transplant (SCT), as determined by the investigator, with an available donor
Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents
Any prior antileukemic therapy for treatment of intermediate, high, very high risk MDS per IPSS-R
Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥ 1 year
Contraindications to azacitidine
Clinical suspicion of active central nervous system (CNS) involvement by MDS
Known active or chronic hepatitis B or C infection or human immunodeficiency virus in medical history
Active hepatitis B virus and/or active hepatitis C virus, and/or HIV following testing at screening
Pregnancy or active breastfeeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35294
2	University of Arkansas for Medical Sciences IRB	Little Rock	Arkansas	United States	72205
3	City of Hope	Duarte	California	United States	91010
4	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
5	UCLA Ronald Reagan Medical Center	Los Angeles	California	United States	90095
6	UC Irvine Health	Orange	California	United States	92868
7	Stanford Cancer Institute	Palo Alto	California	United States	94305
8	University of California, Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
9	University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
10	Moffitt Cancer Center	Tampa	Florida	United States	33612
11	Winship Cancer Institute	Atlanta	Georgia	United States	30322
12	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
13	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
14	University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
15	Tulane Medical Center	New Orleans	Louisiana	United States	70112
16	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
17	Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21231
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
19	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
20	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts	United States	02215
21	University of Michigan Medical School	Ann Arbor	Michigan	United States	48109
22	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota	United States	55455
23	Mid America Division, Inc.	Kansas City	Missouri	United States	64132
24	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri	United States	63110
25	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
26	Weill Cornell Medicine-New York Presbyterian Hospital	New York	New York	United States	10021
27	Mount Sinai Health System	New York	New York	United States	10029
28	Columbia University Medical Center - Herbert Irving Pavilion	New York	New York	United States	10032
29	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
30	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
31	DUHS Duke Cancer Center	Durham	North Carolina	United States	27705
32	The Ohio State University Wexner Medical Center / James Cancer Hospital	Columbus	Ohio	United States	43210
33	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
34	Oregon Health & Science University Pharmacy Services	Portland	Oregon	United States	97239
35	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
36	Thomas Jefferson University, Sidney Kimmel Cancer Center; Clinical Research Organization	Philadelphia	Pennsylvania	United States	19107
37	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
38	Prisma Health Cancer Center	Greenville	South Carolina	United States	29615
39	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
40	UT Southwestern Medical Center	Dallas	Texas	United States	39090
41	Texas Oncology - Baylor Charles A. Simmons Cancer Center	Dallas	Texas	United States	75246
42	Baylor College of Medicine	Houston	Texas	United States	77030
43	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
44	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
45	Seattle Cancer Care Alliance	Seattle	Washington	United States	98019
46	Swedish Cancer Institute	Seattle	Washington	United States	98104
47	Froedtert Hospital & the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
48	Gosford Hospital	Gosford	New South Wales	Australia	2250
49	Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
50	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
51	Westmead Hospital	Westmead	New South Wales	Australia	2145
52	Icon Cancer Foundation	South Brisbane	Queensland	Australia	4101
53	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
54	Flinders Medical Center	Bedford Park	South Australia	Australia	5042
55	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
56	Eastern Health	Box Hill	Victoria	Australia	3128
57	Monash Medical Centre	Clayton	Victoria	Australia	3168
58	Peninsula Private Hospital	Frankston	Victoria	Australia	3199
59	Barwon Health, University Hospital Geelong	Geelong	Victoria	Australia	3220
60	Cabrini Hospital Malvern	Malvern	Victoria	Australia	3144
61	The Alfred Hospital	Melbourne	Victoria	Australia	3004
62	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
63	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
64	Uniklinikum Salzburg	Salzburg		Austria	5020
65	ZNA Middelheim	Antwerpen		Belgium	2060
66	ULB Hopital Erasme	Brussels		Belgium	1070
67	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
68	UZ Brussel	Brussels		Belgium
69	UZ Leuven	Leuven		Belgium	3000
70	AZ Turnhout, Campus St. Elisabeth	Turnhout		Belgium	2300
71	Chu Ucl Namur Site Godinne	Yvoir-Godinne		Belgium	5530
72	Tom Baker Cancer Centre	Calgary		Canada	T2N 4N2
73	QEII Health Sciences Centre	Halifax		Canada	B3H 2Y9
74	Eastern Regional Health Authority	St. John's		Canada	A1B 3V6
75	University Health Network	Toronto		Canada	M5G 2M9
76	Fakultni nemocnice Olomouc, Hemato-onkologicka klinika	Olomouc		Czechia	77520
77	Fakultni nemocnice Ostrava, Klinika hemato-onkologicka	Ostrava		Czechia	70852
78	Helsinki University Central Hospital	Helsinki		Finland	00290
79	Oulu University Hospital	Oulu		Finland	90220
80	CHU Amiens-Picardie	Amiens Cedex 1		France	80054
81	Hopital Henri Mondor	Creteil		France	94010
82	CHU de Grenoble Alpes	La Tronche		France	38700
83	Institut Paoli Calmettes	Marseille		France
84	Hopital Saint Eloi	Montpellier		France	34295
85	CHU de Nantes	Nantes		France	44000
86	CHU de Nice-l Archet	Nice		France	6200
87	Hopital Saint Louis	Paris		France	75475
88	Institut Gustave Roussy	Paris		France	94805
89	Hopital Haut-Leveque	Pessac Cedex		France	33604
90	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
91	CHU de Poitiers - Hopital de la Miletrie	Poitiers		France	86000
92	CHU de Rennes- Hopital Pontchaillou	Rennes Cedex 9		France	35033
93	Universitatsklinikum Carl Gustav Carus	Dresden		Germany	01307
94	Marien hospital, klinik fur onkologie, hamatologie und palliavmedizin	Duesseldorf		Germany
95	Universitatsklinikum Essen	Essen		Germany	45122
96	Universitat Leipzig	Leipzig		Germany
97	Robert-Bosch-Krankenhaus, GmBH, Hamatologie, Onkologie und Palliativmedizin	Stuttgart		Germany	70376
98	Hong Kong Sanatorium & Hospital	Hong Kong		Hong Kong
99	Princess Margaret Hospital	Hong Kong		Hong Kong
100	Queen Mary Hospital	Hong Kong		Hong Kong
101	The Chinese University of Hong Kong, Prince of Wales Hospital	Hong Kong		Hong Kong
102	Tuen Mun Hospital	Hong Kong		Hong Kong
103	Semmelweis Egyetem Belgyógyászati és Hematológiai Kilnika	Budapest		Hungary	1125
104	Debreceni Egyetem Klinikai Központ	Debrecen		Hungary	4032
105	Petz Aladar Egyetemi Oktato Korhaz II. Belgyogyaszat - Hematologial Osztaly	Gyor		Hungary	9024
106	Kaposi Mor Teaching Hospital	Kaposvar		Hungary
107	Bács-Kiskun Megyei Kórház	Kecskemet		Hungary	6000
108	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza		Hungary	4400
109	University of Pecs	Pecs		Hungary	7624
110	Szent Borbála Hospital	Tatabanya		Hungary	2800
111	SC Ematologica- Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo	Alessandria		Italy	15100
112	U.O Ematologica- ASST degli Spedali Civili di Brescia	Brescia		Italy
113	Azienda Ospedaliero-Universitaria Careggi	Firenze		Italy	50134
114	U.O.C Ematologia - Dipartimento di Medicina Interna, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico	Milan		Italy	20122
115	U.O di Ematologia, Ospedale San Gerardo- ASST Monza	Monza		Italy	20052
116	S. C. Ematologia Azienda Ospedaliero - Universitaria Maggiore Della Carita	Novara		Italy	28100
117	Azienda Ospedaliera Ospedali Riuniti Marche Nord	Pesaro		Italy	61100
118	SC di Oncoematologia - Azienda Ospedaliera Santa Maria	Terni		Italy	05100
119	SC Ematologica, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi	Varese		Italy	21100
120	University Medical Center Groningen	Groningen		Netherlands	9700 RB
121	Medisch Centrum Leeuwarden	Leeuwarden		Netherlands	8934 AD
122	Christchurch Hospital	Christchurch		New Zealand	8011
123	Southern District Health Board	Dunedin		New Zealand	9016
124	Auckland City Hospital	Grafton		New Zealand	1142
125	Waikato Hospital	Hamilton		New Zealand	3240
126	Midcentral District Health Board	Palmerston North		New Zealand	4414
127	Haukeland Universitetssjukehus, seksjon for blodsjukdommar- klinisk studieteam	Bergen		Norway	5021
128	Akershus University Hospital	Loerenskog		Norway	1478
129	Oslo University Hospital	Oslo		Norway	0372
130	Stavanger universitetssjukehus	Stavanger		Norway	4068
131	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Hematologii	Krakow		Poland	31-501
132	Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli	Lublin		Poland	20090
133	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw		Poland	50-367
134	Centro Clinico Academico de Braga, Hospital de Braga, E.P.E	Braga		Portugal	4710
135	Champalimaud Foundation	Lisbon		Portugal	1400 - 038
136	Hospital da Luz	Lisbon		Portugal	1500-650
137	Centro Hospitalar Universitario Sao Joao. E.P.E	Porto		Portugal	4200 319
138	Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE	Porto		Portugal	4200-072
139	Area Sanitaria de Santiago de Compostela y Barbanza. Complejo Hospitalario Universitario de SantiagoD	A Coruña		Spain
140	OSI Araba, Hospital Universitario de Alava, Hospital Txagorritxu	Alava		Spain
141	Hospital del Mar	Barcelona		Spain	08003
142	Hospital Universitari Vall D'Hebron	Barcelona		Spain	08035
143	Institut Catala d'Oncologia Girona	Girona		Spain	17007
144	Institut Catala d'Oncologia, Hospital Duran i Reynals	L´Hospitalet de Llobregat		Spain
145	MD Anderson Cancer Center Madrid	Madrid		Spain	28033
146	Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
147	Hospital Universitario La Paz, Edificio General, 6 Planta. Despacho de Hematologia	Madrid		Spain	28046
148	Hospital Universitario Quironsalud Madrid. Servico de Hematologica y Hemoterapia	Madrid		Spain
149	Hospital Regional Universitario de Malaga	Malaga		Spain
150	Centro Hospitalar Universitario Sao Joao	Pamplona		Spain	31008
151	Complejo Asistencial Universitario de Salamanca- Hospital Clinico Universitario de Salamanca	Salamanca		Spain
152	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
153	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
154	Istituto Oncologico Della Svizzera Italiana- IOSI, EOC, Clinica di Ematologia	Bellinzona		Switzerland	6500
155	University of Bern	Bern		Switzerland	3010
156	Universitaetsspital Zurich - Klinik fur Medizinische Onkologie und Hematologie	Zurich		Switzerland	8091
157	Hematoloji Bilim Dali, Yenimahalle	Ankara		Turkey	06200
158	Gazi Universitesi Tip Fakultesi	Ankara		Turkey	06560
159	Ankara Universitesi Tip Fakultesi Cebeci Hastanesi	Ankara		Turkey	06620
160	Dokuz Eylul Universitesi Tip Fakultesi Onkoloji Enstitusu	Inciralt		Turkey	35340
161	Mersin University Medical	Mersin		Turkey	33110
162	Tekirdag Namik Kemal Universitesi Tip Fakultesi	Tekirdag		Turkey	59100
163	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom	B15 2TH
164	United Lincolnshire Hospital NHS Trust	Boston		United Kingdom	PE21 9QS
165	Kent and Canterbury Hospital- East Kent Hospitals University NHS Foundation Trust	Canterbury		United Kingdom	CT1 3NG
166	Oxford University Hospitals NHS Foundation Trust	Oxford		United Kingdom	OX3 9DU