Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML)

Leukemia Clinical Trial

— QuANTUM-First  

Official title:

A Phase 3, Double-Blind, Placebo-controlled Study of Quizartinib Administered in Combination With Induction and Consolidation Chemotherapy, and Administered as Continuation Therapy in Subjects 18 to 75 Years Old With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (QuANTUM First)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02668653
• Other study ID #: AC220-A-U302
• Secondary ID: 2015-004856-2417
• Status: Completed
• Phase: Phase 3
• Start date: September 1, 2016
• Est. completion date: June 16, 2023

Study information

• Verified date: November 2023
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research.

Adults might be able to join this study after bone marrow tests show they have a certain kind of blood cancer (FLT3-ITD AML).

Participants will have an equal chance of receiving quizartinib or placebo along with their chemotherapy.

Description:

This is a phase 3, randomized, double-blind, placebo-control global study. The purpose of this study is to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as continuation therapy for up to 36 cycles) on overall survival in subjects with FLT3-internal tandem duplication (ITD) positive AML.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 539
• Est. completion date: June 16, 2023
• Est. primary completion date: August 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Must be competent and able to comprehend, sign, and date an Ethics Committee (EC) or Institutional Review Board approved Informed Consent Form (ICF) before performance of any study-specific procedures or tests;

2. Is =18 years or the minimum legal adult age (whichever is greater) and =75 years (at Screening);

3. Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome or a myeloproliferative neoplasm, based on the World Health Organization (WHO) 2008 classification (at Screening);

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (at the time the participant signs their first ICF);

5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of =3% FLT3-ITD/total FLT3);

6. Participant is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol;

7. Adequate renal function defined as:

a. Creatinine clearance >50 mL/min, as calculated with the modified Cockcroft Gault equation

8. Adequate hepatic function defined as:

1. Total serum bilirubin (TBL) =1.5 × upper limit of normal (ULN) unless the participant has documented Gilbert's syndrome or the increase is related to increased unconjugated (indirect) bilirubin due to hemolysis;

2. Serum alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 × ULN;

9. Serum electrolytes within normal limits: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia or ionized calcium) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected;

10. If a woman of childbearing potential, must have a negative serum pregnancy test upon entry into this study and must be willing to use highly effective birth control upon enrollment, during the treatment period and for 6 months following the last dose of investigational drug or cytarabine, whichever is later. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months);

11. If male, must be surgically sterile or willing to use highly effective birth control upon enrollment, during the treatment period, and for 6 months following the last dose of investigational drug or cytarabine, whichever is later.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) positive leukemia (ie, chronic myelogenous leukemia in blast crisis); participants who undergo diagnostic workup for APL and treatment with all-trans retinoic acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must be discontinued before starting induction chemotherapy).

2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;

3. Prior treatment for AML, except for the following allowances:

• Leukapheresis;

• Treatment for hyperleukocytosis with hydroxyurea;

• Cranial radiotherapy for central nervous system (CNS) leukostasis;

• Prophylactic intrathecal chemotherapy;

• Growth factor/cytokine support;

4. Prior treatment with quizartinib or other FLT3-ITD inhibitors;

5. Prior treatment with any investigational drug or device within 30 days prior to Randomization (within 2 weeks for investigational or approved immunotherapy) or currently participating in other investigational procedures;

6. History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for participants with symptoms of CNS leukemia to rule out extramedullary CNS involvement;

7. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for at least 2 years;

8. Uncontrolled or significant cardiovascular disease, including any of the following:

• Bradycardia of less than 50 beats per minute, unless the participant has a pacemaker;

• Fridericia's Heart Rate Correction Formula (QTcF) interval >450 msec;

• Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);

• Systolic blood pressure =180 mmHg or diastolic blood pressure =110 mmHg;

• History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);

• History of second (Mobitz II) or third degree heart block (participants with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);

• History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;

• History of New York Heart Association Class 3 or 4 heart failure;

• Known history of left ventricular ejection fraction (LVEF) =45% or less than the institutional lower limit of normal;

• Complete left bundle branch block;

9. Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;

10. Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C);

11. Known history of human immunodeficiency virus (HIV). Participants should be tested for HIV prior to Randomization if required by local regulations or EC;

12. History of hypersensitivity to any excipients in the quizartinib/placebo tablets;

13. Females who are pregnant or breastfeeding;

14. Otherwise considered inappropriate for the study by the Investigator.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Chemotherapy

• Quizartinib

• Placebo

Locations

Country	Name	City	State
Argentina	Sanatorio Allende	Córdoba
Argentina	Sanatorio Britanico	Rosario	Santa Fe
Australia	Townsville Hospital (TTH)	Douglas	Queensland
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	UCL Mont-Godinne	Yvoir
Brazil	Hospital Amaral Carvalho	Brasília
Brazil	Hospital do CEPON	Brasília
Brazil	Instituto do Cancer do Estado de São Paulo	Brasília
Brazil	Santa Casa de Misericórdia de Porto Alegre	Brasília
Brazil	Hospital da Cidade de Passo Fundo	Passo Fundo
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Bulgaria	University Multiprofile Hospital for Active Treatment "Dr. G. Stranski" EAD	Pleven
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD	Sofia
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Vancouver General Hospital (VGH)	Vancouver	British Columbia
China	Peking University First Hospital	Beijing
China	The General Hospital of People's Liberation Army (301 Hospital)	Beijing
China	Fujian Medical University Union Hospital	Fuzhou
China	Guangdong General Hospital	Guangzhou
China	Lanzhou University Second Hospital	Lanzhou
China	Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School	Shanghai
China	West China Hospital, Sichuan University	Taiyuan
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	Tang Du Hospital, Fourth Military Medical University	Xi'an
China	Henan Cancer Hospital	Zhengzhou
Croatia	Klinicka Bolnica Dubrava	Zagreb
Croatia	Klinicka Bolnica Merkur	Zagreb
Croatia	Klinicki Bolnicki Centar Zagreb	Zagreb
Czechia	Fakultní Nemocnice Hradec Králové	Hradec Kralove
Czechia	Fakultní Nemocnice Olomouc	Olomouc
Czechia	Fakultní Nemocnice Ostrava	Ostrava
Czechia	Fakultni Nemocnice Plzen	Plzen
Czechia	Vseobecna Fakultni Nemocnice, Ustav hematologie a krevni transfuze (UHKT)	Praha 2
France	Hospital A. Michallon	Grenoble
France	Centre Hospitalier de Versailles - Hôpital André Mignot	Le Chesnay
France	Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez	Lille
France	Centre Léon Bérard	Lyon
France	L'Institut Paoli - Calmettes	Marguerittes
France	Hôpital de la Conception	Marseille
France	CHRU Montpellier - Saint Eloi	Montpellier
France	Hôpital Saint-Antoine	Paris
France	Hôpital Saint-Louis	Paris
France	Hôpital Haut-Lévêque	Pessac
France	Centre Hospitalier Lyon-Sud	Pierre Benite
France	Centre Henri Becquerel - Centre de Lutte Contre le Cancer	Rouen
France	Centre Hospitalier Universitaire de Toulouse - Hôpital Purpan	Toulouse
Germany	HELIOS Klinikum Bad Saarow	Bad Saarow
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Städtisches Klinikum Braunschweig gGmbH	Braunschweig
Germany	Marien Hospital Düsseldorf GmbH	Düsseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main
Germany	Universitätsklinikum Halle (Saale)	Halle
Germany	Evangelisches Krankenhaus Hamm gGmbH	Hamm
Germany	Medizinische Hochschule Hannover (MHH)	Hannöver
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Münster	Heidelberg
Germany	Universitätsklinikum Tübingen	Heidelberg
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen
Germany	HELIOS Klinikum Wuppertal	Wuppertal
Hong Kong	Prince of Wales Hospital	Shatin
Hungary	Markusovszky Egyetemi Oktatókórház	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szegedi Tudományegyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen
Hungary	Pecsi Tudomanyegyetem Klinikai Központ	Pécs
Hungary	Markusovszky Egyetemi Oktatókórház	Szombathely
Israel	Assaf Harofeh Medical Center	Be'er Ya'aqov	Tsifrin
Israel	Bnai Zion Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah University Medical Center	Jerusalem
Israel	Rabin Medical Center - Beilinson Hospital	Peta? Tiqwa
Israel	The Chaim Sheba Medical Center	Ramat-Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Nazionale SS.Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Azienda Sanitaria Locale 13 - Ospedale "C. e G. Mazzoni"- Ascoli Piceno	Ascoli Piceno
Italy	Azienda Ospedaliero - Universitaria Consorziale Policlinico di Bari	Bari
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna
Italy	IRCCS AOU San Martino - IST	Genova
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	A.O.R.N. "A. Cardarelli"	Napoli
Italy	Azienda Ospedaliero Universitaria Maggiore della Carità di Novara	Novara
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano
Italy	Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello	Palermo
Italy	Ospedale S. Maria delle Croci - Ravenna	Ravenna
Italy	Azienda Ospedaliera Universitaria "Federico II"	Roma
Italy	Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara	Roma
Italy	Azienda Ospedaliero-Universitaria Careggi	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	IRCCS Ospedale San Raffaele	Roma
Italy	Ospedale S. Eugenio	Roma
Italy	Policlinico Tor Vergata	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona	Salerno
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Italy	Azienda Ospedaliera Ordine Mauriziano di Torino	Torino
Italy	Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette	Torino
Italy	ASST dei Sette Laghi - Ospedale di Circolo e Fondazione Macchi Varese	Varese
Japan	Akita University Hospital	Akita
Japan	Aomori Prefectural Central Hospital	Aomori
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital	Bunkyo-Ku	Tokyo
Japan	Chiba Aoba Municipal Hospital	Chiba
Japan	Kameda Medical Center - Kameda General Hospital	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Chugoku Central Hospital	Fukuyama	Hiroshima
Japan	Gifu Municipal Hospital	Gifu
Japan	Hamamatsu University Hospital	Hamamatsu	Shizuoka
Japan	Kyushu University Hospital	Higashi	Fukuoka
Japan	National Hospital Organization Kagoshima Medical Center	Kagoshima
Japan	Kobe City Medical Center General Hospital	Kobe
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	Gunmaken Saiseikai Maebashi Hospital	Maebashi	Gunma
Japan	Ehime Prefectural Central Hospital	Matsuyama	Ehime
Japan	The Jikei University Hospital	Minato-Ku	Tokyo
Japan	Nagasaki University Hospital	Nagasaki
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi
Japan	Osaka City General Hospital	Osaka
Japan	Osaka Red Cross Hospital	Osaka
Japan	Sapporo Hokuyu Hospital	Sapporo	Hokkaido
Japan	National Hospital Organization Sendai Medical Center	Sendai	Miagi
Japan	Tenri Hospital	Tenri	Nara
Japan	NTT Medical Center Tokyo	Tokyo
Japan	Toyohashi Municipal Hospital	Toyohashi	Aichi
Japan	Yokohama City University Hospital	Yokohama	Kanagawa
Japan	University of Fukui Hospital	Yoshida	Fukui
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	SoonChunHyang University Seoul Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Sowon
Korea, Republic of	Ulsan University Hospital (UUH)	Ulsan
Poland	Szpital Uniwersytecki w Krakowie	Kraków
Poland	Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka	Slupsk
Poland	Instytut Hematologii i Transfuzjologi	Warszawa
Poland	Samodzielny Publiczny Szpital Kliniczny Nr. 1 we Wroclawiu	Warszawa
Portugal	Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra	Coimbra
Portugal	Centro Hospitalar Lisboa Central, EPE - Hospital Santo António dos Capuchos	Lisboa
Portugal	Centro Hospitalar de São João, EPE - Hospital de São João	Porto
Portugal	Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António	Porto
Portugal	Instituto Português Oncologia do Porto Francisco Gentil, EPE	Porto
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Institutul Regional de Oncologie Ia?i	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Romania	Spitalul Clinic Coltea	Bucuresti
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucuresti
Romania	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj-Napoca
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova
Romania	Spitalul Clinic Judetean de Urgenta Târgu-Mures (4005)	Târgu-Mures
Romania	Spitalul Clinic Judetean de Urgenta Târgu-Mures (4008)	Târgu-Mures
Russian Federation	Nizhny Novgorod Regional Clinical Hospital	Nizhny Novgorod
Russian Federation	Penza Regional Oncology Dispensary	Penza
Russian Federation	Republican Hospital n.a.V.A. Baranov	Petrozavodsk
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan'
Russian Federation	Almazov Federal North-West Medical Research Centre	Saint Petersburg
Russian Federation	Saratov State Medical University named after V.I. Razumovsky	Saratov
Russian Federation	Leningrad Regional Clinic and Hospital	St. Petersburg
Russian Federation	Russian Research Institute of Hematology and Blood Transfusion	St. Petersburg
Russian Federation	Tula Regional Clinical Hospital	Tula
Serbia	Klinicki Centar Srbije	Belgrade
Serbia	Klinicki Centar Niš	Nis
Serbia	Klinicki Centar Vojvodine	Novi Sad
Singapore	National University Hospital (S) Pte Ltd	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Complejo Hospitalario Universitario de Albacete - Hospital General Universitario	Albacete
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Catalan Institute of Oncology (ICO)	Badalona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Duran i Reynals	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Girona
Spain	Complejo Hospitalario Universitario Granada	Granada
Spain	Complexo Hospitalario Universitario A Coruña	La Coruña
Spain	Hospital Dr. Negrín	Las Palmas De Gran Canaria
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Quirón Madrid	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda
Spain	Hospital Regional Universitario de Málaga - Hospital General	Málaga
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Universitari Son Espases	Palma	Mallorca
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Fundación Jiménez Díaz	Pamplona
Spain	Hospital Álvaro Cunqueiro	Pamplona
Spain	Hospital Clínico Universitario "Lozano Blesa"	Pamplona
Spain	Hospital General Universitario Morales Meseguer	Pamplona
Spain	Hospital Universitario Miguel Servet	Pamplona
Spain	Hosp Universitario Salamanca	Salamanca
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitari Joan XXIII de Tarragona	Tarragona
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Taiwan	Chang Gung Medical Foundation - Kaohsiung Branch	Kaohsiung	Niaosong District
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou Branch	Taoyuan
Ukraine	Cherkasy Regional Oncology Dispensary	Cherkasy
Ukraine	Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho	Poltava
Ukraine	Vinnitsa Regional Clinical Hospital im. N.I. Pirogov	Vinnytsia
Ukraine	Zhitomir Regional Clinical Hospital	Zhytomyr
United Kingdom	Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital	Maidstone
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	Duke Clinical Research Institute	Durham	North Carolina
United States	University of Florida (UF) Health Shands Hospital	Gainesville	Florida
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Franciscan St. Francis Health Indianapolis	Indianapolis	Indiana
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	West Virginia University Hospitals, Inc.	Morgantown	West Virginia
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	NY Medical College - Hudson Valley Hematology Oncology Associates	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Croatia,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Singapore,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Overall survival is defined as the time from randomization until death from any cause.	Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment
Secondary	Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Event-free survival (EFS) is the time from randomization to the earliest date of either refractory disease (or treatment failure [TF]), relapse, or death from any cause. Refractory disease is defined as complete remission never achieved during Induction (CR: >1000 neutrophils, >100,000 platelets, <5% blasts, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts]). For refractory disease, EFS event date is Day 1 (randomization). Relapse after CR is defined as =5% blasts, leukemic blasts, extramedullary leukemia, and presence of rods. This analysis is based on a response assessment with TF defined as not achieving response of CR, using a 42- day window from the start of the last cycle in Induction for CR evaluation.	Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment
Secondary	Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Complete remission (CR) rate is defined as the percentage of participants achieving CR, defined as a disappearance of all target lesions, after Induction.	Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
Secondary	Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Composite complete remission (CRc) rate is defined as the percentage of participants whose best response is complete remission (CR), defined as a disappearance of all target lesions, or CR with incomplete neutrophil or platelet recovery (CRi) at the end of first Induction cycle.	Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
Secondary	Number of Participants With Treatment-emergent Adverse Events Occurring in =10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	A treatment-emergent adverse event (TEAE) is defined as an adverse event that occur, having been absent before first dose of quizartinib or placebo, or have worsened in severity after initiating quizartinib or placebo. Adverse events collected more than 30 days after the last dose of quizartinib/placebo will not be considered TEAEs unless they are considered drug-related.	Date of first dose up to 30 days after last dose, up to 36 cycles following continuation (approximately 6 years 11 months, each cycle is 28 days)
Secondary	Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Complete remission (CR) is defined as participants achieving CR defined as a disappearance of all target lesions. Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.	Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)
Secondary	Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Composite complete remission (CRc) is defined as participants achieving complete remission (CR), defined as a disappearance of all target lesions, or CR with incomplete neutrophil or platelet recovery (CRi). Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.	Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)
Secondary	Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State	AUCss was assessed by population PK analysis during Cycle 1 of each phase.	Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Secondary	Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max)	Css,max was assessed by population PK analysis during Cycle 1 of each phase.	Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Secondary	Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss)	Tmax,ss was assessed by population PK analysis during Cycle 1 of each phase.	Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)