Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

NCT02920008 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SGI-110-06
• Study Type: interventional
• Target: 302
• Locations: 15 countries
• Sites: 95

Brief Summary

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Participants will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone:

• High intensity (intermediate or high dose cytarabine \[HiDAC\]; mitoxantrone, etoposide, and cytarabine \[MEC\]; or fludarabine, cytarabine, granulocyte colony stimulating factor \[G-CSF\], +/- idarubicin \[FLAG/FLAG-Ida\]).
• Low intensity (low dose cytarabine \[LDAC\], decitabine, or azacitidine).
• BSC.

Conditions

Acute Myeloid Leukemia

Keywords

AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.

  From the date of randomization until the date of death, or approximately 34 months

Secondary Outcomes (13)

• Event-Free Survival

  From the date of randomization until the date of death, or approximately 38 months

• Long-Term Survival

  Up to approximately 38 months

• Number of Days Alive and Out of the Hospital (NDAOH)

  6 months

• Transfusion Independence Rate

  Baseline up to approximately 38 months

• Complete Response Rate

  Baseline to end of treatment, or approximately 38 months

Study Arms (2)

guadecitabine

EXPERIMENTAL

Guadecitabine will be given SC at a dose of 60 mg/m\^2 in 28-day cycles (delayed as necessary to allow blood count recovery).

Drug: guadecitabine

Treatment Choice (TC)

ACTIVE COMPARATOR

1. High intensity 2. Low intensity 3. Best supportive care (BSC).

Drug: Treatment Choice (TC)

Interventions

guadecitabine DRUG

In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. In Cycle 2, the guadecitabine dose will be 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by Day ≥28.

Also known as: SGI-110

guadecitabine

Treatment Choice (TC) DRUG

* High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida). * Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine. * Best Supportive Care (BSC).

Treatment Choice (TC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult participants ≥18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
• History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow \[BM\] or peripheral blood \[PB\] blast counts ≥20%).
• Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.
• Participants with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
• Participants must have either PB or BM blasts ≥5% at time of randomization.
• Creatinine clearance or glomerular filtration rate ≥30 mL/min as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas, such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
• Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment of guadecitabine, decitabine, or azacitidine and for at least 3 months after completing treatment and (b) while receiving treatment with high-intensity TC or LDAC and for at least 6 months after completing treatment.

You may not qualify if:

• Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.
• Participants who are in first relapse after initial induction, if they had a response duration of \>12 months from date when first response first documented or if they are good candidates for HCT.
• BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
• Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.
• Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine.
• Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
• Treated with any investigational therapy within 2 weeks of the first dose of study treatment.
• Total serum bilirubin \>2.5 × upper limit of normal (ULN; except for participants with Gilbert's Syndrome for whom direct bilirubin is \<2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
• 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 participant to high risk of noncompliance with the protocol.
• Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring \>2 liters per minute (LPM) oxygen, or any other condition that puts the participant at an imminent risk of death.
• Participants with high PB blasts \>50% AND poor ECOG PS of 2.

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (95)

University of Southern California

Los Angeles, California, 90033, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Franciscan Research Center

Indianapolis, Indiana, 46237, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601-1915, United States

Location

University of New Mexico School of Medicine

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104-5418, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19111-2433, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor Research Institute

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

West Virginia University Hospitals, Inc.

Morgantown, West Virginia, 26506, United States

Location

AZ Sint-Jan Brugge-Oostende AV

Bruges, 8000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2V2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Hopital Maisonneuve Rosemont

Montreal, H1T 2M4, Canada

Location

Aarhus University Hospital

Aarhus C, 8000, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

Location

Hôpital de la Conception

Marseille, 13385, France

Location

CHRU Montpellier - Saint Eloi

Montpellier, 34295, France

Location

Groupe Hospitalier de la Région de Mulhouse et Sud Alsace

Mulhouse, 68100, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69310, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31059, France

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 4103, Germany

Location

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, 38114, Germany

Location

Marien Hospital Düsseldorf GmbH

Düsseldorf, 40479, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, 6120, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Medizinischen Fakultät Mannheim der Universität Heidelberg

Mannheim, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

SE ÁOK I. sz. Belgyógyászati Klinika

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

Location

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, 7400, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Központ

Pécs, Hungary

Location

Szegedi Tudományegyetem

Szeged, 6725, Hungary

Location

IRCCS AOU San Martino - IST

Genova, 16132, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Ospedale San Raffaele - Milano

Milan, 20132, Italy

Location

A.O.R.N. "A. Cardarelli"

Napoli, 80131, Italy

Location

A.S.U Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia

Udine, 33100, Italy

Location

Akita University Hospital

Akita, 010-8543, Japan

Location

Chugoku Central Hospital

Fukuyama-Shi, 720-0001, Japan

Location

Tokai University Hospital

Isehara-shi, 259-1193, Japan

Location

Saitama Medical Center

Kawagoe-Shi, 350-8550, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650-0047, Japan

Location

Japanese Red Cross Kyoto Daini Hospital

Kyoto, 602-8026, Japan

Location

University Hospital, Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Gunmaken Saiseikai Maebashi Hospital

Maebashi, 371-0821, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

The Japanese Red Cross Nagasaki Genbaku Hospital

Nagasaki, 852-8511, Japan

Location

Kindai University Hospital

Osakasayama-Shi, 589-8511, Japan

Location

Saga University Hospital

Saga, 849-8501, Japan

Location

NTT Medical Center Tokyo

Shinagawa-Ku, 141-8625, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

National Hospital Organization Disaster Medical Center

Tachikawa-Shi, 190-0014, Japan

Location

Yamagata University Hospital

Yamagata, 990-9585, Japan

Location

University of Fukui Hospital

Yoshida-Gun, 910-1193, Japan

Location

Instytut Hematologii i Transfuzjologi

Warsaw, 02-776, Poland

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Severance Hospital

Seoul, 3722, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 6591, South Korea

Location

Ulsan University Hospital (UUH)

Ulsan, 44033, South Korea

Location

Hospital Clínic de Barcelona

Barcelona, 8036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 8041, Spain

Location

Hospital Duran i Reynals

Barcelona, 8907, Spain

Location

Vall d'Hebron Institut d'Oncologia

Barcelona, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Khmelnytskyi Regional Hospital

Khmelnytskyi, 29000, Ukraine

Location

Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho

Poltava, 36011, Ukraine

Location

Heart of England NHS Foundation Trust - Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

East Kent Hospitals University NHS Foundation Trust - Kent and Canterbury Hospital

Canterbury, CT1 3NG, United Kingdom

Location

St. James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (1)

• Roboz GJ, Sanz G, Griffiths EA, Yee K, Kantarjian H, Recher C, Byrne MT, Patkowska E, Kim HJ, Thomas X, Moors I, Stock W, Illes A, Fenaux P, Miyazaki Y, Yamauchi T, O'Connell CL, Hao Y, Keer HN, Azab M, Dohner H. Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial. Blood Adv. 2024 Apr 23;8(8):2020-2029. doi: 10.1182/bloodadvances.2023012062.

  PMID: 38231126 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

clinicaltrialinfo@taihooncology.com

609-250-7336

Study Officials

• Harold N Keer, MD, PhD

  Astex Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2016
• First Posted: September 30, 2016
• Study Start: March 16, 2017
• Primary Completion: January 20, 2020
• Study Completion: June 1, 2020
• Last Updated: August 28, 2024
• Results First Posted: May 25, 2023

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2); HU (5); GB (4); UA (2); BE (3); IT (5); DE (8); KR (7); FR (9); SE (1); ES (11); JP (17); US (15); PL (1); CA (5)