Acute Myeloid Leukemia Clinical Trial
Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia
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).
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).
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.
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.
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There are 89 Locations for this study
Los Angeles California, 90033, United States
Chicago Illinois, 60637, United States
Indianapolis Indiana, 46237, United States
Hackensack New Jersey, 07601, United States
Albuquerque New Mexico, 87106, United States
Buffalo New York, 14263, United States
New York New York, 10021, United States
Durham North Carolina, 27710, United States
Oklahoma City Oklahoma, 73104, United States
Philadelphia Pennsylvania, 19104, United States
Philadelphia Pennsylvania, 19111, United States
Nashville Tennessee, 37232, United States
Dallas Texas, 75246, United States
Houston Texas, 77030, United States
Morgantown West Virginia, 26506, United States
Brugge , 8000, Belgium
Brussels , 1200, Belgium
Gent , 9000, Belgium
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 2, Canada
Toronto Ontario, M5G 2, Canada
Montreal Quebec, H4A 3, Canada
Montreal , H1T 2, Canada
Aarhus C , 8000, Denmark
Copenhagen , 2100, Denmark
Bayonne , 64100, France
Marseille , 13385, France
Montpellier , 34295, France
Mulhouse , 68100, France
Paris , 75475, France
Pessac , 33604, France
Pierre Bénite , 69310, France
Rouen cedex 1 , 76038, France
Toulouse , 31059, France
Leipzig Sachsen, 4103, Germany
Braunschweig , 38114, Germany
Düsseldorf , 40479, Germany
Halle , 6120, Germany
Kiel , 24105, Germany
Mannheim , , Germany
Muenchen , 81377, Germany
Ulm , 89081, Germany
Budapest , 1083, Hungary
Debrecen , 4032, Hungary
Kaposvar , 7400, Hungary
Pécs , , Hungary
Szeged , 6725, Hungary
Genova , 16132, Italy
Milano , 20122, Italy
Milano , 20132, Italy
Napoli , 80131, Italy
Udine , 33100, Italy
Akita-shi , 010-8, Japan
Fukuyama-Shi , 720-0, Japan
Isehara-shi , 259-1, Japan
Kawagoe-Shi , 350-8, Japan
Kobe-shi , 650-0, Japan
Kyoto-shi , 602-8, Japan
Kyoto-shi , 602-8, Japan
Maebashi-shi , 371-0, Japan
Nagasaki-shi , 852-8, Japan
Nagasaki-Shi , 852-8, Japan
Osakasayama-Shi , 589-8, Japan
Saga-shi , 849-8, Japan
Shinagawa-Ku , 141-8, Japan
Shizuoka , 411-8, Japan
Tachikawa-Shi , 190-0, Japan
Yamagata-Shi , 990-9, Japan
Yoshida-Gun , 910-1, Japan
Busan , 49241, Korea, Republic of
Seoul , 3080, Korea, Republic of
Seoul , 3722, Korea, Republic of
Seoul , 5505, Korea, Republic of
Seoul , 6351, Korea, Republic of
Seoul , 6591, Korea, Republic of
Ulsan , 44033, Korea, Republic of
Warszawa , 02-77, Poland
Barcelona , 8036, Spain
Barcelona , 8041, Spain
Barcelona , 8907, Spain
Barcelona , , Spain
Cáceres , 10003, Spain
Córdoba , 14004, Spain
Madrid , 28007, Spain
Oviedo , 33011, Spain
Sevilla , 41013, Spain
Valencia , 46017, Spain
Valencia , 46026, Spain
Göteborg , 413 4, Sweden
Khmelnytskyi , 29000, Ukraine
Poltava , 36011, Ukraine
Birmingham , B9 5S, United Kingdom
Bristol , BS2 8, United Kingdom
Canterbury , CT1 3, United Kingdom
Leeds , LS9 7, United Kingdom
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