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

A Phase 3, Multicenter, Open-label, Randomized Study of SGI-110 Versus Treatment Choice (TC) in Adults With Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Considered Candidates for Intensive Remission Induction Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: SGI-110 (guadecitabine); Drug: Treatment Choice

• Study Type: Interventional
• Enrollment (Actual): 815
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Heidelberg, Victoria, Australia
      • Austin Health
• Austria
  • Styria
    • Graz, Styria, Austria
      • Medizinische Universität Graz
  • Vienna
    • Wien, Vienna, Austria
      • Hanusch Krankenhaus Wiener Gebietskrankenkasse
• Belgium
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6061
      • Grand Hôpital de Charleroi
  • Oost-vlaanderen
    • Ghent, Oost-vlaanderen, Belgium, 9000
      • UZ Gent
  • West-vlaanderen
    • Brugge, West-vlaanderen, Belgium, 8000
      • Algemeen Ziekenhuis Sint-Jan
• Bulgaria
  • Plovdiv, Bulgaria
    • UMHAT 'Sveti Georgi' EAD
  • Varna, Bulgaria
    • Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center
    • Edmonton, Alberta, Canada, 76B 2B7
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
• Czechia
  • Praha 10, Czechia, Praha 10
    • Fakultni nemocnice Kralovske Vinohrady
  • Jihormoravsky KRAJ
    • Brno, Jihormoravsky KRAJ, Czechia
      • Fakultni Nemocnice Brno
  • Praha
    • Praha 2, Praha, Czechia
      • Vseobecna fakultni nemocnice v Praze
• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet-Copenhagen University Hospital
  • Odense, Denmark
    • Odense University Hospital
• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital
  • Southern Finland
    • Tampere, Southern Finland, Finland
      • Tampere University Hospital
• France
  • Alsace
    • Mulhouse Cedex, Alsace, France
      • GHR Mulhouse Sud-Alsace
  • Aquitaine
    • Bayonne, Aquitaine, France
      • Hôpital Hôtel-Dieu
  • Haute-normandie
    • Rouen Cedex 1, Haute-normandie, France
      • Centre Henri-Becquerel
  • Ile-de-france
    • Paris Cedex 10, Ile-de-france, France, 75010
      • Hôpital Saint Louis
  • Limousin, Lorraine
    • Limoges Cedex, Limousin, Lorraine, France, 87000
      • CHRU de Limoges - Hôpital Dupuytren
  • Midi-pyrenees
    • Toulouse cedex 9, Midi-pyrenees, France
      • Centre Hospitalier Universitaire de Toulouse
  • PAYS DE LA Loire
    • Nantes cedex 1, PAYS DE LA Loire, France
      • Hôpital Hôtel-Dieu
  • Provence Alpes COTE D'azur
    • Marseille Cedex 9, Provence Alpes COTE D'azur, France
      • Institut Paoli Calmettes
    • Nice, Provence Alpes COTE D'azur, France
      • Centre Antoine Lacassagne
  • Rhone-alpes
    • La Tronche, Rhone-alpes, France, 38700
      • Centre Hospitalier Universitaire Grenoble
    • Lyon Cedex 08, Rhone-alpes, France
      • Centre Leon Berard
    • Pierre Bénite Cedex, Rhone-alpes, France
      • Centre Hospitalier Lyon Sud
• Germany
  • Baden-wuerttemberg
    • Freiburg, Baden-wuerttemberg, Germany
      • Universitaetsklinikum Freiburg
    • Ulm, Baden-wuerttemberg, Germany
      • Universitatsklinikum Ulm
    • Villingen-Schwenningen, Baden-wuerttemberg, Germany
      • Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
  • Hessen
    • Frankfurt am Main, Hessen, Germany
      • Universitätsklinikum Frankfurt Goethe Universität
  • Niedersachsen
    • Braunschweig, Niedersachsen, Germany, 38114
      • Städtisches Klinikum Braunschweig gGmbH
  • Nordrhein-westfalen
    • Düsseldorf, Nordrhein-westfalen, Germany
      • Marien Hospital Dusseldorf GMBH
  • Schleswig-holstein
    • Kiel, Schleswig-holstein, Germany
      • Universitätsklinikum Schleswig-Holstein
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mór Oktató Kórház
  • Bacs-kiskun
    • Kecskemét, Bacs-kiskun, Hungary
      • Bacs-kiskun Megyei Korhaz
• Italy
  • Alessandria, Italy
    • Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
  • Busto Arsizio, Italy, 21052
    • Azienda Ospedaliera Ospedale di Busto Arsizio
  • Catania, Italy
    • Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto-Santo Bambino
  • Genova, Italy
    • IRCCS Azienda Ospedaliera Universitaria San Martino - IST
  • Milano, Italy
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Modena, Italy
    • Azienda Ospedaliero-Universitaria Policlinico di Modena
  • Napoli, Italy
    • AORN A. Cardarelli
  • Roma, Italy
    • Azienda Policlinico Umberto I di Roma
  • Udine, Italy
    • Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine
  • Pesaro E Urbino
    • Pesaro, Pesaro E Urbino, Italy
      • Azienda Ospedaliera Ospedali Riuniti Marche Nord
  • Potenza
    • Rionero in Vulture, Potenza, Italy
      • IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture
  • Torino
    • Orbassano, Torino, Italy
      • Azienda Ospedaliero-Univesitaria San Luigi Gonzaga
• Japan
  • Chubu, Japan
  • Chugoku, Japan
  • Kanto, Japan
  • Kinki, Japan
  • Kyushu, Japan
  • Tohoku, Japan
• Korea, Republic of
  • Busan, Korea, Republic of
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of
    • Seoul Saint Mary's Hospital
  • Ulsan, Korea, Republic of
    • Ulsan University Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • Seoul National University Bundang Hospital
  • Jeollanam-do
    • Hwasun, Jeollanam-do, Korea, Republic of
      • Chonnam National University Hwasun Hospital
  • Seoul
    • Jongno Gu, Seoul, Korea, Republic of
      • Seoul National University Hospital
• Netherlands
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland
      • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
  • Lodzkie
    • Lódz, Lodzkie, Poland
      • Wojewodzki Szpital Specjalistyczny im. M. Kopernika
  • Lubelskie
    • Lublin, Lubelskie, Poland
      • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland
      • Instytut Hematologii i Transfuzjologii
    • Warszawa, Mazowieckie, Poland
      • Samodzielny Publiczny Centralny Szpital Kliniczny
  • Opolskie
    • Opole, Opolskie, Poland
      • Szpital Wojewódzki w Opolu - Samodzielny Publiczny Zaklad Opieki Zdrowotnej
  • Slaskie
    • Chorzów, Slaskie, Poland
      • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
• Romania
  • Iasi, Romania
    • Institutul Regional de Oncologie Iasi
  • Mures
    • Targu-Mures, Mures, Romania
      • Spitalul Clinic Judetean de Urgenta Tirgu-Mures
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Sverdlovsk Regional Clinical Hospital #1
  • Ryazan, Russian Federation
    • Ryazan Regional Clinical Hospital
  • Saratov, Russian Federation
    • Saratov State Medical University
• Serbia
  • Belgrade, Serbia
    • Clinical Center of Serbia
  • Novi Sad, Serbia
    • Clinical Centre of Vojvodina
• Spain
  • Barcelona, Spain
    • Hospital Vall d´hebron
  • Caceres, Spain
    • Hospital San Pedro de Alcántara
  • Granada, Spain
    • Hospital General Virgen de las Nieves
  • Madrid, Spain
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Salamanca, Spain
    • Hospital Clínico Universitario de Salamanca
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Asturias
    • Oviedo, Asturias, Spain
      • Hospital Universitario Central de Asturias
  • Barcelona
    • Badalona, Barcelona, Spain
      • Hospital Universitari Germans Trias i Pujol
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital Huddinge
  • Skane
    • Lund, Skane, Sweden
      • Skanes Universitetssjukhus I Lund
• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • Mackay Memorial Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan
    • Tao-Yuan, Taoyuan, Taiwan
      • Chang Gung Medical Foundation-Linkou Branch
• United Kingdom
  • England
    • London, England, United Kingdom
      • Chelsea And Westminster Hospital NHS Foundation Trust
    • London, England, United Kingdom
      • King's College Hospital
  • Kent
    • Gillingham, Kent, United Kingdom
      • Medway Maritime Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Cancer Center
  • California
    • La Jolla, California, United States
      • Scripps Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Westwood, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10065
      • Columbia University Medical Center
    • Stony Brook, New York, United States, 11790
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States
      • Duke Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Cleveland, Ohio, United States
      • University Hospitals Monarch Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SGI-110 (guadecitabine); Guadecitabine 60 mg/m^2 administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.	Drug: SGI-110 (guadecitabine); Investigational medicinal product
Active Comparator: 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.	Drug: Treatment Choice; Choice of one: cytarabine, decitabine, or azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Complete Response (CR)	Number of participants with a best response of CR assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.	Up to 38 months (median follow-up of 25.5 months)
Overall Survival	Survival time was defined as the number of days from the day the participant was randomly assigned to study treatment to the date of death, regardless of cause.	At 676 death events (up to 38 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Composite CR (CRc)	CRc is reported as the number of participants with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi).	Up to 38 months (median follow-up of 25.5 months)
Number of Days Alive and Out of the Hospital	The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital (NDAOH) was calculated as: NDAOH=180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.	Month 6
Progression-free Survival (PFS)	Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, participant receiving an alternative anti-leukemia therapy (including hematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause.	Up to 38 months (median follow-up of 25.5 months)
Number of Red Blood Cell or Platelet Transfusions	The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.	Month 6
Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-5D-5L	EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. Mean change in scores from baseline are summarized in which an index score of 0 represents the worst health state and 1 represents the best health state.	Baseline to Month 6
Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-VAS	EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarized.	Baseline to Month 6
Duration of CR	Duration of CR (in number of days) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or ≥ 5% leukemic blasts in BM.	Up to 38 months (median follow-up of 25.5 months)

Collaborators and Investigators

• Sponsor: Astex Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2015
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): June 17, 2019

Study Registration Dates

• First Submitted: January 22, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; SGI-110; DNA Hypomethylating Agen
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Guadecitabine
• Other Study ID Numbers: SGI-110-04