An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia

A Phase III, Double-Blind, Placebo-Controlled, Multicenter, Randomized Study Of Pracinostat In Combination With Azacitidine In Patients ≥18 Years With Newly Diagnosed Acute Myeloid Leukemia Unfit For Standard Induction Chemotherapy

This is a Phase III, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (AZA) as background therapy in patients ≥ 18 years of age with newly diagnosed acute myeloid leukemia (AML), excluding acute promyelocytic leukemia and cytogenetic low-risk AML, who are unfit to receive intensive remission induction chemotherapy due to age ≥ 75 years or comorbidities. Patients will be randomized in a 1:1 ratio to one of two groups: Group A (experimental group) to receive pracinostat plus AZA and Group B (control group) to receive placebo plus AZA. Randomization will be stratified by cytogenetic risk category (intermediate vs. unfavorable-risk, according to SWOG Cytogenetic Risk Category Definitions) and ECOG performance status (0-1 vs. 2). Treatments will be administered based on 28-day cycles, with pracinostat/placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and AZA administered for 7 days of each cycle. Study treatment should continue until there is documented disease progression, relapse from complete remission (CR), or non-manageable toxicity. A minimum of 6 cycles may be required to achieve a complete remission. Once permanently discontinued from study treatment, patients will enter the Long-term Follow-up phase of the study and will be followed for assessment of disease progression, if applicable, and survival every 3 months (±1 month) until death. The end of this study is defined when 390 events (deaths) have occurred and the study is unblinded for final overall survival analysis. Patients who are receiving study treatment at the end of the study may have the opportunity to continue to receive the study drugs to which they were randomized to (Post- Study Observation Period), until the Sponsor informs the Investigators of the appropriate course of action based on the study results. The Post-Study Observation Period is defined as the period starting from the end of the study for a maximum of 12 months.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Azacitidine; Drug: Pracinostat; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000JHQ
    • Sanatorio Allende
  • Córdoba, Argentina, X5016KEH
    • H ospi tal Privado de Cordoba
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1181ACH
      • Hospital Italiano de Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1426ANZ
      • Instituto Médico Especializado Alexander Fleming
    • La Plata, Buenos Aires, Argentina, B1900AXI
      • Hospital Italiano La Plata
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Sanatorio Britanico SA Paraguay 40, 3P
• Australia
  • Liverpool, Australia, 2170
    • Liverpool Hospital
  • Perth, Australia, 6000
    • Royal Perth Hospital
  • Randwick, Australia, 2031
    • Prince of Wales Hospital
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Epping, Victoria, Australia, 3076
      • The Northern hospital Pharmacy Department, Ground Floor
    • Geelong, Victoria, Australia, 3220
      • Barwon Health, University Hospital Geelong
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital, Clinical Trial Pharmacy
• Austria
  • Linz, Austria, 4020
    • Krankenhaus der Elisabethinen Linz GmbH
  • Salzburg, Austria, 5020
    • Müllner Hauptstrabe 48
  • Vienna, Austria, 1130
    • General Hospital Hietzing
• Brazil
  • Barretos, Brazil, 1478-400
    • Hospital de Cancer de Barretos
  • Belo Horizonte, Brazil, 30.150-221
    • Hospital Santa Casa de Belo Horizonte -Serviyo de Oncologia Clinica
  • Florianópolis, Brazil, 88034-000
    • Centro de Pesquisas Oncológicas - CEPON
  • Porto Alegre, Brazil, 90035-903
    • Hospital de ClÃ-nicas de Porto Alegre
  • Rio De Janeiro, Brazil, 20231-050
    • Institute Nacional de Cancer Jose de Alencar Gomes da Silva-INCA
  • Santo André, Brazil, 09060-870
    • Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Oncologia
  • São José Do Rio Preto, Brazil, 15090-000
    • Hospital de Base de São José do Rio Preto
  • Paranà
    • Curitiba, Paranà, Brazil, 81520-060
      • Liga Paranaense de Com bate ao Cancer - Hospital Erasto Gaertner
  • SP
    • Jau, SP, Brazil, 17210-080
      • Ce ntro de Pesquisas Hospital Amara l Ca rvalh o
    • São Paulo, SP, Brazil, 0827-120
      • Centro de Pesquisa Clinica do Hospital Santa Marcelina
• Czechia
  • Hradec Králové, Czechia, 5oo 05
    • "Fakultni nemocnice Hradec Kralove,
  • Olomouc, Czechia, 77900
    • Fakultni nemocnice Olomuc
  • Praha, Czechia, 100 34
    • "Fakultni nemocnice Kralovske Vinohrady,
  • Praha, Czechia, 10034
    • Fakultni nemocnice Kralovske Vinohrady,
  • Praha 2, Czechia, I28 08
    • Vseobecna fakultni nemocnice
• France
  • Amiens, France, 800054
    • CHU Amiens Picardie-Site Sud-Service d'Hematologie
  • Nantes, France, 44277
    • L'Hopital Prive du Confluent SAS
  • Nice, France
    • CHU de Nice, Archet 1 Hospital-Hematology department
  • Paris, France, 75475
    • Hospital saints Louis
  • Pessac, France, 33604
    • Haut-Leveque-Service d'hématologie clinique et de thérapie cellular
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rouen Cedex 1, France, 76028
    • Centre Henri Becquerel
• Germany
  • Berlin, Germany, 10117
    • Charité-Universitätsmedizin - 1. Campus Mitte
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz gGmbH
  • Gera, Germany, 07548
    • SRH Wald-Klinikum Gera GmbH
  • Kiel, Germany, 24116
    • Staedtisches Krankenhaus Kiel
  • Mainz, Germany, 55131
    • Universitaet Mainz
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Universitätsklinikum Erlangen
  • Bayern
    • Amberg, Bayern, Germany, 92224
      • Klinikum St. Marien Amberg
  • North Rhine-westphalia
    • Herne, North Rhine-westphalia, Germany, 44625
      • Marien Hospital Herne-Universitätsklinikum der Ruhr-Universität Bochum
• Hungary
  • Budapest, Hungary, H-1097
    • St. Istvan & St. Laszlo Hospital, Deapartment of Hematology and Stem Cell Transplantation
  • Debrecen, Hungary, H-4032
    • University of Debrecen Clinical Center
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz, Dep. Of Haematology
  • Nyiregyhaza, Hungary, II-1065
    • Szabolcs-Szatmar-Bereg megyei Korhazak es Egyetemi Oktatokorhaz â€" Josa Andras Oktatokorhaz, Hematologiai Osztaly
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • University of Pecs
    • Pécs, Baranya, Hungary, H-7624
      • Pecsi Egyetem I. Belgy6gyaszati Klinika
• Italy
  • Bari, Italy, 70124
    • AOU Policlinico Consorziale di Bari
  • Bologna, Italy, 40138
    • AOU Policlinico Sant'Orsola-Malpighi
  • Firenze, Italy, 50134
    • Azienda Ospedaliera-Università Careggi
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino
  • Lecce, Italy, 73100
    • Ospedale Vito Fazzi
  • Naples, Italy, 80131
    • Azienda Ospedaliere Antonio Cardarelli,
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo Pavia
  • Roma, Italy, 00133
    • Fondazione PTV-Policlinico Tor Vergata
  • Roma, Italy, 00168
    • Policlinico Universitario Gemelli
  • Torino, Italy, 10128
    • Azienda Ospedaliera Ordine Mauriziano
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele-U.O. Ematologia e TMO
  • PA
    • Palermo, PA, Italy, 90146
      • Ospedale la Maddalena, UO Oncoematologia e TMO
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Hwasun, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil medical center, div hematology
  • Seoul, Korea, Republic of, 0080
    • Seoul National University Hospital, Div.Hematology/Oncology
  • Seoul, Korea, Republic of, 06351
    • Sumsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St.Mary Hospital, div hemato-oncology
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital
• Poland
  • Poznań, Poland, 60-192
    • Examen Sp. Z o.o.,
  • Wałbrzych, Poland, 58-309
    • Specjalistyc:my Szpi tal im. dra Alfreda Sokolowskiego
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny
  • Łódź, Poland, 93-513
    • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
• Romania
  • Bucuresti, Romania, 020125
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 030171
    • clinical hospital Coltea Bld
  • Bucuresti, Romania, 050098
    • Spitalul Universitar de Urgenta Bucuresti
  • Cluj-Napoca, Romania, 400015
    • Oncological Institute "Ion Chiricuta"
  • Iaşi, Romania, 700483
    • institutu Regional de Oncologie Iasi
  • Jud.dolj
    • Craiova, Jud.dolj, Romania, 200143
      • Spitalul Clinic Filantropia
• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • "Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • Hospital Univers itario HM Sanchinarro
  • Salamanca, Spain, 37007
    • Hospital Uni vcrsitario de Salamanca
  • Sevilla, Spain, 46013
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico de La Fe
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Catala d'Oncologia (ICO)
  • Extremadura
    • Caceres, Extremadura, Spain, 10003
      • Hospital San Pedro de Alcántara
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Hosp.Universitario A Coruña-Hospital Teresa Herrera
  • Isla Baleares
    • Palma De Mallorca, Isla Baleares, Spain, 07120
      • Hospital Universitario Son Espases
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital
  • Changhua, Taiwan, 500
    • Hematology and Oncology, Changhwa Christian Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospita
  • Taipei, Taiwan, 100
    • Division of Hematology, National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Koo-Foundation Sun Yat-Sen Cancer Center
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Teaching Hospitals NHS Foundation Trust
  • Coventry, United Kingdom, CV2 2DX
    • University Hospitals Coventry and Warwickshire NHS Trust
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
  • Devon
    • Exeter, Devon, United Kingdom, EX25DW
      • Royal Devon & Exeter Hospital (Wonford site)
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Blackpool Teaching Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Tempe, Arizona, United States, 85284
      • Arizona Oncology Associates, East Valley Cancer Center
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center-North Campus
  • California
    • La Jolla, California, United States, 92037
      • 10666 N.Torrey Pines-Scripps Cancer Center
    • La Jolla, California, United States, 92093-0698
      • UC San Diego Moores Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint alphonsus Regional medical center-cancer care center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Universitz of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute, St. Matthews Campus
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Pontchartrain Cancer Center (Research Location)
  • Maryland
    • Bethesda, Maryland, United States, 20187
      • Rcca Md Llc
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial medical center-university campus
  • Michigan
    • Farmington Hills, Michigan, United States, 48336
      • Michigan Center of Medical Research
    • Lansing, Michigan, United States, 48910
      • Michigan State University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Mercy Research
  • Montana
    • Joplin, Montana, United States, 64804
      • 100 Mercy Way
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center-2400 Pratt Street
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital Cleveland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Clinic Oncology & Hematology
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialist and Research Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • GHS Cancer Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75216
      • VA North texas Health Care sytem,Dallas VA Medical Center div. Hematology Oncology
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Emily Couric Clinical Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98108
      • Thomas Reeve Chauncey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patient ≥ 18 years of age with newly diagnosed, histologically or cytologically confirmed, AML including de novo, secondary to antecedent hematologic disorders, or treatment-related disease with intermediate or unfavorable-risk cytogenetics

2. Unable to receive intensive chemotherapy regimens at enrollment, based on one of the following:

   I. Age ≥ 75 years, or

   II. Age < 75 years with at least 1 of the following co-morbidities:

   1. An ECOG performance status of 2
   2. Clinically significant cardiovascular disease defined as:

   i. Left ventricular ejection fraction (LVEF) ≤ 50%, measured within 3 months prior to Day 1 confirmed by ECHO/MUGA ii. Congestive heart failure requiring medical therapy iii. Chronic stable angina requiring medical therapy iv. Prior cerebrovascular accident with sequelae c. Clinically significant pulmonary disease defined as: i. Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected ii. Lung diffusing capacity for carbon monoxide (DLCO) ≤ 65% of expected Confirmed by pulmonary tests. d. Diabetes mellitus with symptomatic end-organ damage (e.g., retinopathy, nephropathy, neuropathy, vasculopathy) e. Autoimmune inflammatory conditions (e.g., rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease, or similar) requiring chronic disease modifying therapy (e.g., etanercept, adalimumab, infliximab, rituximab, methotrexate, or similar) f. Class III obesity defined as a Body Mass Index (BMI) > 40 kg/m2 g. Renal impairment defined as serum creatinine > 1.3 mg/dL (> 115 µmol/L) or creatinine clearance <70 ml/min h. Clinically significant cognitive impairment defined as requiring medical therapy and/or assistance with activities of daily living

3. 20% blasts in bone marrow
4. Peripheral white blood cell (WBC) count 30,000/µL For cyto-reduction, hydroxyurea is allowed during screening and up to Cycle 1, Days 1-14, to reduce WBC count to < 30,000 µL prior to Day 1. After Cycle 1, Day 14, hydroxyurea is prohibited.
5. ECOG performance status ≤ 2

6. Adequate organ function as evidenced by the following laboratory findings:

   1. Total bilirubin ≤ 2 × upper limit of normal (ULN) or < 3 x ULN for patients with Gilbert-Meulengracht Syndrome
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
7. Serum creatinine ≤ 1.5 × ULN according to institutional standards or creatinine clearance ≥ 50 mL/min
8. QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 ms on electrocardiogram (ECG) at Screening
9. Male patient who is surgically sterile, or male patient who is willing to agree to remain completely abstinent (refrain from heterosexual intercourse) or who use barrier contraceptive measures and agree to refrain from donating sperm during the entire study treatment period and for 3 months after the last administration of study drug
10. Female patient who is of childbearing potential willing to use adequate contraceptive measures while participating on study, OR willing to completely abstain from heterosexual intercourse during the entire study treatment period
11. Female patient who is of childbearing potential must have a negative serum pregnancy test result within 3 weeks prior to starting study drugs.
12. Willing to provide voluntary written informed consent before performance of any study related procedure not part of normal medical care
13. Willing and able to understand the nature of this study and to comply with the study and follow-up procedures.

Exclusion Criteria:

1. Able to receive intensive induction chemotherapy
2. AML-associated inv(16)/t(16;16)/del(16q), t(15;17) (i.e. promyelocytic leukemia) with/without secondary aberrations; t(8;21) lacking del (9q) or complex karyotypes
3. Presence of an active malignant disease within the last 12 months, with the exception of adequately treated cervical cancer in-situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]). Other malignancies may be considered after consultation with the Medical Monitor
4. Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety or put the study outcomes at risk
5. Uncontrolled arrhythmias; any Class 3-4 cardiac diseases as defined by the New York Heart Association (NYHA) functional classification
6. Evidence of AML central nervous system (CNS) involvement

7. Previous chemotherapy for AML except for the following, which are allowed:

   1. Hydroxyurea for cytoreduction
   2. One course of hypomethylating agent therapy (i.e.; up to 7 doses of azacitidine or 3-5 days of decitabine) within 30 days prior to enrollment (Day 1)
8. Use of experimental drugs ≤ 30 days prior to screening
9. Received prior HDAC inhibitor therapy
10. Received prior treatment with a hypomethylating agent, except as allowed in Exclusion Criterion 7.b
11. Known hypersensitivity to any components of pracinostat, azacitidine, or mannitol
12. History of human immunodeficiency virus (HIV) or an active and uncontrolled infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
13. Gastrointestinal (GI) tract disease that causes an inability to take oral medication, malabsorption syndrome, or a requirement for IV alimentation; prior surgical procedures affecting absorption; or uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
14. Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition, that contraindicates the use of pracinostat and/or AZA, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study
15. Breast-feeding woman
16. current smokers(use of patches, chewing gums and vaping nicotine conaining fluids is permitted). Patients who stopped smoking at least 8 day prior to first pracinostat dosing can be enrolled, provided they refrain from smoking during the whole study
17. prohibited concomitant medications
18. uncontrolled infections
19. receive more than 1 prior cycle of HMA or bone marrow transplant for any prior hematological disorder antecedent to AML

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pracinostat plus AZA; 60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.	Drug: Azacitidine; SC or IV injection; Other Names: AZA; Drug: Pracinostat; 60 mg capsule; Other Names: SB939
Placebo Comparator: Placebo plus AZA; 1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.	Drug: Azacitidine; SC or IV injection; Other Names: AZA; Drug: Placebos; capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS measures the time from randomization to death due to any cause.	826 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphologic Complete Remission (CR) Rate	The CR rate is the proportion of patients who achieve a morphologic CR according to the response criteria; <5% blasts in a bone marrow aspirate sample with spicules; There should be no blasts with Auer rods; No EMD; Absolute Neutrophil Count (ANC) ≥1,000/μL; Platelet count of ≥100,000/μL; Patient must be independent of transfusions (for at least 1week before each assessment)	744 days
Complete Remission Without Minimal Residual Disease (CRmrd) Rate	proportion of patients who achieve a CR without minimal residual disease by multicolor flow cytometry according to the following criteria; Morphologic CR; Minimal Residual Disease (MRD) by MFC negative	826 days
Cytogenetic Complete Remission (CRc) Rate	The CRc rate is the proportion of patients who achieve a reversion to a normal karyotype at CR within the study period. This endpoint applies only to patients with abnormal cytogenetic at enrollment according to the following criterion Morphologic CR plus reversion to a normal karyotype (defined as no clonal abnormalities detected in a minimum of 20 mitotic cells)	826 days
Transfusion Independence (TI)	Transfusion independence rate is defined as the proportion of patients who show eight weeks or over without red blood cell (RBC-TI) and/or platelet (PLT-TI) transfusion during study period	826 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Remission (cCR) Rate	Composite complete remission (cCR) rate is the proportion of patients who achieve either a disease response of CR, CRi or MLFS (i.e., cCR = CR + CRi + MLFS) within the study period, according to the response criteria	744 days
Duration of Composite Complete Remission	Duration of cCR response is the time from first cCR until documented relapse (the definition of relapse from CR will be applied) or death. Duration of cCR is only defined for patients who achieve a cCR	744 days
Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30)	QLQ-C30 is made of multi-item scales and single-item measures (functional and symptom scales, a global health status/QoL scale and single items). Item range is the difference between possible max and min response to individual items of the scale; most items take values from 1 to 4 (range=3). Global health status takes values from 1 to 7 (range = 6). For statistical analysis purpose, single-item and scale values were all standardized (according to linear transformation described in Scoring Manual) to obtain scores ranging 0-100. An high scale score represents an higher response level. Thus an high score for a functional scale represents an high/healthy level of functioning, an high score for the global health status/QoL represents a high QoL, an high score for a symptom scale/item represents an high level of symptomatology/problems.	from baseline up to 660 days
Relapse Free Survival	the time from the date of achievement of CR or CRi until the date of relapse or death from any cause	744 days
Progressive Free Survival Rate (PFS)	PFS is defined as the time from the date of randomization until the date of relapse (progression), or death from any cause, whichever occurs first.	800 days
Duration of Morphologic CR	Duration of morphologic CR is defined as the time from the date of achievement of CR until the date of relapse (progression).	744 days
Time to CR	Time to CR is defined as the time from the date of randomization until the date of CR in the absence of interceding therapies. The analysis set was the ITT set.	616 days
Morphologic CR Within 6 Cycles Rate	Morphologic CR within 6 cycles rate is defined as the proportion of patients who achieved CR in the absence of interceding therapies within 6 treatment cycles (i.e., during treatment phase up to Day 1 of Cycle 7 included). Analysis was performed in the ITT set.	within 6 cycles

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA
• Collaborators: Clinipace Worldwide
• Investigators: Study Chair: Guillermo Garcia-Manero, MD, MD Anderson

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2017
• Primary Completion (Actual): August 20, 2020
• Study Completion (Actual): August 20, 2020

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: PRAN-16-52

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No