Clinical trial NCT02348489: SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia, Myeloid, Acute
Keywords: AML
Acute Myeloid Leukemia
SGI-110
DNA Hypomethylating Agen
Lead sponsor: Astex Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-28
Enrollment: 815
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With a Complete Response (CR)
timeFrame: Up to 38 months (median follow-up of 25.5 months)
measure: Overall Survival
timeFrame: At 676 death events (up to 38 months)
Secondary outcomes:
measure: Number of Participants With Composite CR (CRc)
timeFrame: Up to 38 months (median follow-up of 25.5 months)
measure: Number of Days Alive and Out of the Hospital
timeFrame: Month 6
measure: Progression-free Survival (PFS)
timeFrame: Up to 38 months (median follow-up of 25.5 months)
measure: Number of Red Blood Cell or Platelet Transfusions
timeFrame: Month 6
measure: Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-5D-5L
timeFrame: Baseline to Month 6
measure: Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-VAS
timeFrame: Baseline to Month 6
measure: Duration of CR
timeFrame: Up to 38 months (median follow-up of 25.5 months)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Monarch Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Styria
city: Wien
country: Austria
facility: Hanusch Krankenhaus Wiener Gebietskrankenkasse
state: Vienna
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
state: Hainaut
city: Ghent
country: Belgium
facility: UZ Gent
state: Oost-vlaanderen
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan
state: West-vlaanderen
city: Plovdiv
country: Bulgaria
facility: UMHAT 'Sveti Georgi' EAD
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno
state: Jihormoravsky KRAJ
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
state: Praha
city: Praha 10
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet-Copenhagen University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
state: Southern Finland
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Mulhouse Cedex
country: France
facility: GHR Mulhouse Sud-Alsace
state: Alsace
city: Bayonne
country: France
facility: Hôpital Hôtel-Dieu
state: Aquitaine
city: Rouen Cedex 1
country: France
facility: Centre Henri-Becquerel
state: Haute-normandie
city: Paris Cedex 10
country: France
facility: Hôpital Saint Louis
state: Ile-de-france
city: Limoges Cedex
country: France
facility: CHRU de Limoges - Hôpital Dupuytren
state: Limousin, Lorraine
city: Toulouse cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse
state: Midi-pyrenees
city: Nantes cedex 1
country: France
facility: Hôpital Hôtel-Dieu
state: PAYS DE LA Loire
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
state: Provence Alpes COTE D'azur
city: Nice
country: France
facility: Centre Antoine Lacassagne
state: Provence Alpes COTE D'azur
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire Grenoble
state: Rhone-alpes
city: Lyon Cedex 08
country: France
facility: Centre Léon Bérard
state: Rhone-alpes
city: Pierre Bénite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone-alpes
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden-wuerttemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-wuerttemberg
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
state: Baden-wuerttemberg
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt Goethe Universität
state: Hessen
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH
state: Niedersachsen
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf GmbH
state: Nordrhein-westfalen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-holstein
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz
state: Bacs-kiskun
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord
state: Pesaro E Urbino
city: Rionero in Vulture
country: Italy
facility: IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture
state: Potenza
city: Orbassano
country: Italy
facility: Azienda Ospedaliero-Univesitaria San Luigi Gonzaga
state: Torino
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
city: Busto Arsizio
country: Italy
facility: Azienda Ospedaliera Ospedale di Busto Arsizio
city: Catania
country: Italy
facility: Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto-Santo Bambino
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino - IST
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena
city: Napoli
country: Italy
facility: AORN A. Cardarelli
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I di Roma
city: Udine
country: Italy
facility: Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine
city: Chubu
country: Japan
city: Chugoku
country: Japan
city: Kanto
country: Japan
city: Kinki
country: Japan
city: Kyushu
country: Japan
city: Tohoku
country: Japan
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Jongno Gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
state: Dolnoslaskie
city: Lódz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika
state: Lodzkie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
state: Lubelskie
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny
state: Mazowieckie
city: Opole
country: Poland
facility: Szpital Wojewódzki w Opolu - Samodzielny Publiczny Zaklad Opieki Zdrowotnej
state: Opolskie
city: Chorzów
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól Szpitali Miejskich
state: Slaskie
city: Targu-Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Tirgu-Mures
state: Mures
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital #1
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebrón
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Granada
country: Spain
facility: Hospital General Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus i Lund
state: Skane
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Tao-Yuan
country: Taiwan
facility: Chang Gung Medical Foundation-LinKou Branch
state: Taoyuan
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
state: Kent
Study officials:
References: