Acute Myeloid Leukemia Clinical Trial

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

Summary

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Subjects 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.

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Full Description

This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and safety of guadecitabine in adults with previously treated acute myeloid leukemia (AML) will be conducted in approximately 20 countries. There will be a 14-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last approximately 2 years. Duration of individual participant participation will vary, and participants may continue to receive treatment for as long as they continue to benefit.

Approximately 404 participants from approximately 100 study centers will be randomly assigned to either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 participants per group). TC is as follows:

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).

Guadecitabine will be given subcutaneous (SC) at a dose of 60 microgram per meter square (mg/m^2) in 28-day cycles. In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. Cycle 2 will be either the 5-day regimen (Days 1-5) or 10-day regimen (Days 1-5 and 8-12) based on assessment of disease response and hematologic recovery at the end of Cycle 1. In subsequent cycles, guadecitabine treatment will be for 5 days only (Days 1-5).

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 3

Estimated Enrollment:

302

Study ID:

NCT02920008

Recruitment Status:

Completed

Sponsor:

Astex Pharmaceuticals, Inc.

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There are 89 Locations for this study

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University of Southern California
Los Angeles California, 90033, United States
The University of Chicago Medical Center
Chicago Illinois, 60637, United States
Franciscan Research Center
Indianapolis Indiana, 46237, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack New Jersey, 07601, United States
University of New Mexico School of Medicine
Albuquerque New Mexico, 87106, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Weill Cornell Medical College
New York New York, 10021, United States
Duke Cancer Institute
Durham North Carolina, 27710, United States
University of Oklahoma Medical Center
Oklahoma City Oklahoma, 73104, United States
Hospital of the University of Pennsylvania
Philadelphia Pennsylvania, 19104, United States
Temple University Hospital
Philadelphia Pennsylvania, 19111, United States
Vanderbilt University Medical Center
Nashville Tennessee, 37232, United States
Baylor Research Institute
Dallas Texas, 75246, United States
MD Anderson Cancer Center
Houston Texas, 77030, United States
West Virginia University Hospitals, Inc.
Morgantown West Virginia, 26506, United States
AZ Sint-Jan Brugge-Oostende AV
Brugge , 8000, Belgium
Cliniques Universitaires Saint-Luc
Brussels , 1200, Belgium
Universitair Ziekenhuis Gent
Gent , 9000, Belgium
Tom Baker Cancer Centre
Calgary Alberta, T2N 4, Canada
University of Alberta Hospital
Edmonton Alberta, T6G 2, Canada
Princess Margaret Cancer Centre
Toronto Ontario, M5G 2, Canada
McGill University Health Centre
Montreal Quebec, H4A 3, Canada
Hopital Maisonneuve Rosemont
Montreal , H1T 2, Canada
Aarhus University Hospital
Aarhus C , 8000, Denmark
Rigshospitalet
Copenhagen , 2100, Denmark
Centre Hospitalier de la Côte Basque
Bayonne , 64100, France
Hôpital de la Conception
Marseille , 13385, France
CHRU Montpellier - Saint Eloi
Montpellier , 34295, France
Groupe Hospitalier de la Région de Mulhouse et Sud Alsace
Mulhouse , 68100, France
Hôpital Saint-Louis
Paris , 75475, France
CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
Pessac , 33604, France
Centre Hospitalier Lyon-Sud
Pierre Bénite , 69310, France
Centre Henri Becquerel
Rouen cedex 1 , 76038, France
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse , 31059, France
Universitätsklinikum Leipzig
Leipzig Sachsen, 4103, Germany
Städtisches Klinikum Braunschweig gGmbH
Braunschweig , 38114, Germany
Marien Hospital Düsseldorf GmbH
Düsseldorf , 40479, Germany
Universitätsklinikum Halle (Saale)
Halle , 6120, Germany
Universitätsklinikum Schleswig-Holstein
Kiel , 24105, Germany
Medizinischen Fakultät Mannheim der Universität Heidelberg
Mannheim , , Germany
Klinikum der Universität München
Muenchen , 81377, Germany
Universitätsklinikum Ulm
Ulm , 89081, Germany
SE ÁOK I. sz. Belgyógyászati Klinika
Budapest , 1083, Hungary
Debreceni Egyetem Klinikai Központ
Debrecen , 4032, Hungary
Somogy Megyei Kaposi Mór Oktató Kórház
Kaposvar , 7400, Hungary
Pecsi Tudomanyegyetem Klinikai Központ
Pécs , , Hungary
Szegedi Tudományegyetem
Szeged , 6725, Hungary
IRCCS AOU San Martino - IST
Genova , 16132, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milano , 20122, Italy
Ospedale San Raffaele - Milano
Milano , 20132, Italy
A.O.R.N. "A. Cardarelli"
Napoli , 80131, Italy
A.S.U Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia
Udine , 33100, Italy
Akita University Hospital
Akita-shi , 010-8, Japan
Chugoku Central Hospital
Fukuyama-Shi , 720-0, Japan
Tokai University Hospital
Isehara-shi , 259-1, Japan
Saitama Medical Center
Kawagoe-Shi , 350-8, Japan
Kobe City Medical Center General Hospital
Kobe-shi , 650-0, Japan
Japanese Red Cross Kyoto Daini Hospital
Kyoto-shi , 602-8, Japan
University Hospital, Kyoto Prefectural University of Medicine
Kyoto-shi , 602-8, Japan
Gunmaken Saiseikai Maebashi Hospital
Maebashi-shi , 371-0, Japan
Nagasaki University Hospital
Nagasaki-shi , 852-8, Japan
The Japanese Red Cross Nagasaki Genbaku Hospital
Nagasaki-Shi , 852-8, Japan
Kindai University Hospital
Osakasayama-Shi , 589-8, Japan
Saga University Hospital
Saga-shi , 849-8, Japan
NTT Medical Center Tokyo
Shinagawa-Ku , 141-8, Japan
Shizuoka Cancer Center
Shizuoka , 411-8, Japan
National Hospital Organization Disaster Medical Center
Tachikawa-Shi , 190-0, Japan
Yamagata University Hospital
Yamagata-Shi , 990-9, Japan
University of Fukui Hospital
Yoshida-Gun , 910-1, Japan
Pusan National University Hospital
Busan , 49241, Korea, Republic of
Seoul National University Hospital
Seoul , 3080, Korea, Republic of
Severance Hospital
Seoul , 3722, Korea, Republic of
Asan Medical Center
Seoul , 5505, Korea, Republic of
Samsung Medical Center
Seoul , 6351, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul , 6591, Korea, Republic of
Ulsan University Hospital (UUH)
Ulsan , 44033, Korea, Republic of
Instytut Hematologii i Transfuzjologi
Warszawa , 02-77, Poland
Hospital Clínic de Barcelona
Barcelona , 8036, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona , 8041, Spain
Hospital Duran i Reynals
Barcelona , 8907, Spain
Vall d'Hebron Institut d'Oncologia
Barcelona , , Spain
Hospital San Pedro de Alcántara
Cáceres , 10003, Spain
Hospital Universitario Reina Sofía
Córdoba , 14004, Spain
Hospital General Universitario Gregorio Marañón
Madrid , 28007, Spain
Hospital Universitario Central de Asturias
Oviedo , 33011, Spain
Hospital Universitario Virgen del Rocío
Sevilla , 41013, Spain
Hospital Universitario Dr. Peset
Valencia , 46017, Spain
Hospital Universitari i Politècnic La Fe
Valencia , 46026, Spain
Sahlgrenska University Hospital
Göteborg , 413 4, Sweden
Khmelnytskyi Regional Hospital
Khmelnytskyi , 29000, Ukraine
Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho
Poltava , 36011, Ukraine
Heart of England NHS Foundation Trust - Heartlands Hospital
Birmingham , B9 5S, United Kingdom
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
Bristol , BS2 8, United Kingdom
East Kent Hospitals University NHS Foundation Trust - Kent and Canterbury Hospital
Canterbury , CT1 3, United Kingdom
St. James's University Hospital
Leeds , LS9 7, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 3

Estimated Enrollment:

302

Study ID:

NCT02920008

Recruitment Status:

Completed

Sponsor:


Astex Pharmaceuticals, Inc.

How clear is this clinincal trial information?

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