SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction

NCT ID: NCT02348489

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 815 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-19
• Study Completion Date: 2019-06-17

Brief Summary

To compare efficacy and safety between SGI-110 and Treatment Choice in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy.

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SGI-110 (guadecitabine)

Guadecitabine 60 mg/m\^2 administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Group Type: EXPERIMENTAL

SGI-110 (guadecitabine)

Intervention Type: DRUG

Investigational medicinal product

Treatment Choice

One of the following treatment regimens: 20 mg cytarabine administered subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m\^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m\^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.

Group Type: ACTIVE_COMPARATOR

Treatment Choice

Intervention Type: DRUG

Choice of one: cytarabine, decitabine, or azacitidine

Interventions

SGI-110 (guadecitabine)

Investigational medicinal product

Intervention Type: DRUG

Treatment Choice

Choice of one: cytarabine, decitabine, or azacitidine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) according to World Health Organization (WHO) classification.

Performance status (ECOG) of 0-3. Adults with previously untreated AML except for hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for myelodysplastic syndrome (MDS) is allowed.

Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on EITHER:

1. ≥75 years of age OR

2. <75 years of age with at least 1 of the following:

i. Poor performance status (ECOG) score of 2-3.

ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:

1. Left ventricular ejection fraction (LVEF) ≤50%.

2. Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected.

3. Forced expiratory volume in 1 second (FEV1) ≤65% of expected.

4. Chronic stable angina or congestive heart failure controlled with medication.

iii. Liver transaminases >3 × upper limit of normal (ULN).

iv. Other contraindication(s) to anthracycline therapy (must be documented).

v. Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the study medical monitor before randomization.

Creatinine clearance as estimated by the Cockcroft-Gault (C-G) or other medically acceptable formulas ≥30 mL/min.

Exclusion Criteria

Candidate for intensive remission induction chemotherapy at the time of enrollment.

Candidate for best supportive care only, ie, not a candidate for any active therapy with the TC comparators.

Known extramedullary central nervous system (CNS) AML.

Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.

Prior treatment with decitabine or azacitidine.

Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.

Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.

Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.

Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or advanced pulmonary disease requiring >2 liters per minute (LPM) oxygen.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospitals Monarch Medical Center

Cleveland, Ohio, United States

Mayo Clinic Cancer Center

Scottsdale, Arizona, United States

Scripps Cancer Center

La Jolla, California, United States

University of Southern California

Los Angeles, California, United States

University of Chicago

Chicago, Illinois, United States

University of Kansas Medical Center

Westwood, Kansas, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

John Theurer Cancer Center at Hackensack

Hackensack, New Jersey, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Weill Cornell Medical College

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Duke Cancer Center

Durham, North Carolina, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Temple University

Philadelphia, Pennsylvania, United States

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Medizinische Universität Graz

Graz, Styria, Austria

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Vienna, Vienna, Austria

Grand Hôpital de Charleroi

Charleroi, Hainaut, Belgium

UZ Gent

Ghent, Oost-vlaanderen, Belgium

Algemeen Ziekenhuis Sint-Jan

Bruges, West-vlaanderen, Belgium

UMHAT 'Sveti Georgi' EAD

Plovdiv, , Bulgaria

Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD

Varna, , Bulgaria

Tom Baker Cancer Center

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Fakultní nemocnice Brno

Brno, Jihormoravsky KRAJ, Czechia

Všeobecná fakultní nemocnice v Praze

Prague, Prague, Czechia

Fakultní nemocnice Královské Vinohrady

Prague, , Czechia

Aarhus University Hospital

Aarhus, , Denmark

Rigshospitalet-Copenhagen University Hospital

Copenhagen, , Denmark

Odense University Hospital

Odense, , Denmark

Tampere University Hospital

Tampere, Southern Finland, Finland

Helsinki University Central Hospital

Helsinki, , Finland

GHR Mulhouse Sud-Alsace

Mulhouse, Alsace, France

Hôpital Hôtel-Dieu

Bayonne, Aquitaine, France

Centre Hospitalier Universitaire Grenoble

La Tronche, Auvergne-Rhône-Alpes, France

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Centre Henri-Becquerel

Rouen, Haute-normandie, France

CHRU de Limoges - Hôpital Dupuytren

Limoges, Limousin, Lorraine, France

Centre Hospitalier Universitaire de Toulouse

Toulouse, Midi-pyrenees, France

Hôpital Hôtel-Dieu

Nantes, Pays de la Loire Region, France

Institut Paoli Calmettes

Marseille, Provence-Alpes-Côte d'Azur Region, France

Centre Antoine Lacassagne

Nice, Provence-Alpes-Côte d'Azur Region, France

Hôpital Saint Louis

Paris, Île-de-France Region, France

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, Baden-Wurttemberg, Germany

Universitätsklinikum Frankfurt Goethe Universität

Frankfurt am Main, Hesse, Germany

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, Lower Saxony, Germany

Marien Hospital Düsseldorf GmbH

Düsseldorf, North Rhine-Westphalia, Germany

Universitätsklinikum Schleswig-Holstein

Kiel, Schleswig-Holstein, Germany

Bacs-Kiskun Megyei Korhaz

Kecskemét, Bács-Kiskun county, Hungary

Semmelweis Egyetem

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, , Hungary

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, Pesaro E Urbino, Italy

IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture

Rionero in Vulture, Potenza, Italy

Azienda Ospedaliero-Univesitaria San Luigi Gonzaga

Orbassano, Torino, Italy

Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria

Alessandria, , Italy

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, , Italy

Azienda Ospedaliera Ospedale di Busto Arsizio

Busto Arsizio, , Italy

Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto-Santo Bambino

Catania, , Italy

IRCCS Azienda Ospedaliera Universitaria San Martino - IST

Genova, , Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, , Italy

AORN A. Cardarelli

Napoli, , Italy

Azienda Policlinico Umberto I di Roma

Roma, , Italy

Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine

Udine, , Italy

Chugoku, , Japan

Chūbu, , Japan

Kanto, , Japan

Kinki, , Japan

Kyushu, , Japan

Tōhoku, , Japan

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, Poland

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, Lublin Voivodeship, Poland

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, Poland

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Masovian Voivodeship, Poland

Szpital Wojewódzki w Opolu - Samodzielny Publiczny Zaklad Opieki Zdrowotnej

Opole, Opole Voivodeship, Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól Szpitali Miejskich

Chorzów, Silesian Voivodeship, Poland

Wojewodzki Szpital Specjalistyczny im. M. Kopernika

Lódz, Łódź Voivodeship, Poland

Spitalul Clinic Judetean de Urgenta Tirgu-Mures

Târgu Mureş, Mureș County, Romania

Institutul Regional de Oncologie Iasi

Iași, , Romania

Ryazan Regional Clinical Hospital

Ryazan, , Russia

Saratov State Medical University

Saratov, , Russia

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, , Russia

Clinical Center of Serbia

Belgrade, , Serbia

Clinical Centre of Vojvodina

Novi Sad, , Serbia

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Seoul National University Hospital

Jongno Gu, Seoul, South Korea

Inje University Busan Paik Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul Saint Mary's Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Vall d´Hebrón

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital General Virgen de las Nieves

Granada, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Skånes Universitetssjukhus i Lund

Lund, Skåne County, Sweden

Karolinska University Hospital Huddinge

Stockholm, , Sweden

Chang Gung Medical Foundation-LinKou Branch

Taoyuan District, Taoyuan, Taiwan

China Medical University Hospital

Taichung, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chelsea and Westminster Hospital NHS Foundation Trust

London, England, United Kingdom

King's College Hospital

London, England, United Kingdom

Medway Maritime Hospital

Gillingham, Kent, United Kingdom

Countries

United States; Australia; Austria; Belgium; Bulgaria; Canada; Czechia; Denmark; Finland; France; Germany; Hungary; Italy; Japan; Netherlands; Poland; Romania; Russia; Serbia; South Korea; Spain; Sweden; Taiwan; United Kingdom

References

Fenaux P, Gobbi M, Kropf PL, Issa JJ, Roboz GJ, Mayer J, Krauter J, Robak T, Kantarjian H, Novak J, Jedrzejczak WW, Thomas X, Ojeda-Uribe M, Miyazaki Y, Min YH, Yeh SP, Brandwein J, Gercheva-Kyuchukova L, Demeter J, Griffiths E, Yee K, Dohner K, Hao Y, Keer H, Azab M, Dohner H. Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia: a global phase 3 randomized study. Blood Adv. 2023 Sep 12;7(17):5027-5037. doi: 10.1182/bloodadvances.2023010179.

Reference Type: DERIVED

PMID: 37276510 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SGI-110-04

Identifier Type: -

Identifier Source: org_study_id