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

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02348489
• Other study ID #: SGI-110-04
• Status: Completed
• Phase: Phase 3
• Start date: March 19, 2015
• Est. completion date: June 17, 2019

Study information

• Verified date: December 2020
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 815
• Est. completion date: June 17, 2019
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• SGI-110 (guadecitabine)
Investigational medicinal product
• Treatment Choice
Choice of one: cytarabine, decitabine, or azacitidine

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Austria	Medizinische Universität Graz	Graz	Styria
Austria	Hanusch Krankenhaus Wiener Gebietskrankenkasse	Wien	Vienna
Belgium	Algemeen Ziekenhuis Sint-Jan	Brugge	West-vlaanderen
Belgium	Grand Hôpital de Charleroi	Charleroi	Hainaut
Belgium	UZ Gent	Ghent	Oost-vlaanderen
Bulgaria	UMHAT 'Sveti Georgi' EAD	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD	Varna
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Czechia	Fakultní nemocnice Brno	Brno	Jihormoravsky KRAJ
Czechia	Fakultní nemocnice Královské Vinohrady	Praha 10
Czechia	Všeobecná fakultní nemocnice v Praze	Praha 2	Praha
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet-Copenhagen University Hospital	Copenhagen
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Central Hospital	Helsinki
Finland	Tampere University Hospital	Tampere	Southern Finland
France	Hôpital Hôtel-Dieu	Bayonne	Aquitaine
France	Centre Hospitalier Universitaire Grenoble	La Tronche	Rhone-alpes
France	CHRU de Limoges - Hôpital Dupuytren	Limoges Cedex	Limousin, Lorraine
France	Centre Léon Bérard	Lyon Cedex 08	Rhone-alpes
France	Institut Paoli Calmettes	Marseille Cedex 9	Provence Alpes COTE D'azur
France	GHR Mulhouse Sud-Alsace	Mulhouse Cedex	Alsace
France	Hôpital Hôtel-Dieu	Nantes cedex 1	PAYS DE LA Loire
France	Centre Antoine Lacassagne	Nice	Provence Alpes COTE D'azur
France	Hôpital Saint Louis	Paris Cedex 10	Ile-de-france
France	Centre Hospitalier Lyon Sud	Pierre Bénite Cedex	Rhone-alpes
France	Centre Henri-Becquerel	Rouen Cedex 1	Haute-normandie
France	Centre Hospitalier Universitaire de Toulouse	Toulouse cedex 9	Midi-pyrenees
Germany	Städtisches Klinikum Braunschweig gGmbH	Braunschweig	Niedersachsen
Germany	Marien Hospital Düsseldorf GmbH	Düsseldorf	Nordrhein-westfalen
Germany	Universitätsklinikum Frankfurt Goethe Universität	Frankfurt am Main	Hessen
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden-wuerttemberg
Germany	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-holstein
Germany	Universitätsklinikum Ulm	Ulm	Baden-wuerttemberg
Germany	Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH	Villingen-Schwenningen	Baden-wuerttemberg
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár
Hungary	Bacs-Kiskun Megyei Korhaz	Kecskemét	Bacs-kiskun
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	Milano
Italy	Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena
Italy	AORN A. Cardarelli	Napoli
Italy	Azienda Ospedaliero-Univesitaria San Luigi Gonzaga	Orbassano	Torino
Italy	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 Policlinico Umberto I di Roma	Roma
Italy	Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine	Udine
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do
Korea, Republic of	Seoul National University Hospital	Jongno Gu	Seoul
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul Saint Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól Szpitali Miejskich	Chorzów	Slaskie
Poland	Wojewodzki Szpital Specjalistyczny im. M. Kopernika	Lódz	Lodzkie
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin	Lubelskie
Poland	Szpital Wojewódzki w Opolu - Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Opole	Opolskie
Poland	Instytut Hematologii i Transfuzjologii	Warszawa	Mazowieckie
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny	Warszawa	Mazowieckie
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu	Wroclaw	Dolnoslaskie
Romania	Institutul Regional de Oncologie Iasi	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Tirgu-Mures	Targu-Mures	Mures
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	Saratov State Medical University	Saratov
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Centre of Vojvodina	Novi Sad
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Vall d´Hebrón	Barcelona
Spain	Hospital San Pedro de Alcantara	Caceres
Spain	Hospital General Virgen de las Nieves	Granada
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Sweden	Skånes Universitetssjukhus i Lund	Lund	Skane
Sweden	Karolinska University Hospital Huddinge	Stockholm
Taiwan	China Medical University Hospital	Taichung
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Medical Foundation-LinKou Branch	Tao-Yuan	Taoyuan
United Kingdom	Medway Maritime Hospital	Gillingham	Kent
United Kingdom	Chelsea and Westminster Hospital NHS Foundation Trust	London	England
United Kingdom	King's College Hospital	London	England
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Chicago	Chicago	Illinois
United States	University Hospitals Monarch Medical Center	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Duke Cancer Center	Durham	North Carolina
United States	John Theurer Cancer Center at Hackensack	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Scripps Cancer Center	La Jolla	California
United States	University of Southern California	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Mayo Clinic Cancer Center	Scottsdale	Arizona
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)