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

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)

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Leukemia
• Intervention / Treatment: Drug: Placebo; Drug: Chemotherapy; Drug: Quizartinib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 539
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000JHQ
    • Sanatorio Allende
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CVB
      • Sanatorio Británico
• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville Hospital (TTH)
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge-Oostende AV
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Yvoir, Belgium, 5530
    • UCL Mont-Godinne
• Brazil
  • Brasília, Brazil, 70750-521
    • Hospital Amaral Carvalho
  • Brasília, Brazil, 70750-521
    • Hospital do CEPON
  • Brasília, Brazil, 70750-521
    • Instituto do Cancer do Estado de Sao Paulo
  • Brasília, Brazil, 70750-521
    • Santa Casa de Misericordia de Porto Alegre
  • Passo Fundo, Brazil, 99010-260
    • Hospital da cidade de Passo Fundo
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clínicas de Porto Alegre
• Bulgaria
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment "Dr. G. Stranski" EAD
  • Sofia, Bulgaria, 1000
    • University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G-3G3
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital (VGH)
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Princess Margaret Cancer Centre
• China
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 100853
    • The General Hospital of People's Liberation Army (301 Hospital)
  • Fuzhou, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510030
    • Guangdong General Hospital
  • Lanzhou, China, 730030
    • Lanzhou University Second Hospital
  • Shanghai, China, 200025
    • Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School
  • Taiyuan, China, 30001
    • West China Hospital, Sichuan University
  • Tianjin, China, 300020
    • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
  • Wenzhou, China, 325015
    • The First Affiliated Hospital of Wenzhou Medical University
  • Xi'an, China, 710038
    • Tang Du Hospital, Fourth Military Medical University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• Croatia
  • Zagreb, Croatia, 10000
    • Klinicka bolnica Dubrava
  • Zagreb, Croatia, 10000
    • Klinicki bolnicki centar Zagreb
  • Zagreb, Croatia, 10000
    • Klinicka bolnica Merkur
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Fakultni nemocnice Olomouc
  • Ostrava, Czechia, 708 52
    • Fakultni Nemocnice Ostrava
  • Plzen, Czechia, 304 60
    • Fakultni Nemocnice Plzen
  • Praha 2, Czechia, 128 20
    • Vseobecna Fakultni Nemocnice, Ustav hematologie a krevni transfuze (UHKT)
• France
  • Grenoble, France, 38043
    • Hospital A. Michallon
  • Le Chesnay, France, 78150
    • Centre Hospitalier de Versailles - Hopital Andre Mignot
  • Lille, France, 59037
    • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marguerittes, France, 13009
    • L'Institut Paoli - Calmettes
  • Marseille, France, 13385
    • Hôpital de la Conception
  • Montpellier, France, 34295
    • CHRU Montpellier - Saint Eloi
  • Paris, France, 75012
    • Hopital Saint-Antoine
  • Paris, France, 75475
    • Hopital Saint-Louis
  • Pessac, France, 33604
    • Hôpital Haut-Lévêque
  • Pierre Benite, France, 69495
    • Centre hospitalier Lyon-Sud
  • Rouen, France, 76038
    • Centre Henri Becquerel - Centre de Lutte Contre le Cancer
  • Toulouse, France, 31059
    • Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
• Germany
  • Bad Saarow, Germany, 15526
    • Helios Klinikum Bad Saarow
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Braunschweig, Germany, 38114
    • Städtisches Klinikum Braunschweig gGmbH
  • Düsseldorf, Germany, 40479
    • Marien Hospital Dusseldorf GMBH
  • Essen, Germany, 45122
    • Universitatsklinikum Essen
  • Frankfurt am Main, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Halle, Germany, 6120
    • Universitatsklinikum Halle (Saale)
  • Hamm, Germany, 59063
    • Evangelisches Krankenhaus Hamm gGmbH
  • Hannöver, Germany, 30625
    • Medizinische Hochschule Hannover (MHH)
  • Heidelberg, Germany, 69120
    • UniversitatsKlinikum Heidelberg
  • Heidelberg, Germany, 69115
    • Universitatsklinikum Munster
  • Heidelberg, Germany, 69115
    • Universitatsklinikum Tubingen
  • Leipzig, Germany, 4103
    • Universitätsklinikum Leipzig
  • Mutlangen, Germany, 73557
    • Stauferklinikum Schwäbisch Gmünd
  • Wuppertal, Germany, 42283
    • Helios Klinikum Wuppertal
• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1051
    • Markusovszky Egyetemi Oktatokorhaz
  • Budapest, Hungary, 1051
    • Szegedi Tudomanyegyetem
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Pécs, Hungary, 7624
    • Pécsi Tudományegyetem Klinikai Központ
  • Szombathely, Hungary, 9700
    • Markusovszky Egyetemi Oktatokorhaz
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah University Medical Center
  • Petaẖ Tiqwa, Israel, 49100
    • Rabin Medical Center - Beilinson Hospital
  • Ramat-Gan, Israel, 52621
    • The Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Tsifrin
    • Be'er Ya'aqov, Tsifrin, Israel, 70300
      • Assaf Harofeh Medical Center
• Italy
  • Alessandria, Italy, 15121
    • Azienda Ospedaliera Nazionale SS.Antonio e Biagio e Cesare Arrigo
  • Ascoli Piceno, Italy, 63100
    • Azienda Sanitaria Locale 13 - Ospedale "C. e G. Mazzoni"- Ascoli Piceno
  • Bari, Italy, 70124
    • Azienda Ospedaliero - Universitaria Consorziale Policlinico di Bari
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
  • Genova, Italy, 16132
    • IRCCS AOU San Martino - IST
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Napoli, Italy, 80131
    • A.O.R.N. "A. Cardarelli"
  • Novara, Italy, 28100
    • Azienda Ospedaliero Universitaria Maggiore della Carita di Novara
  • Orbassano, Italy, 10043
    • Azienda Ospedaliero - Universitaria San Luigi Gonzaga
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
  • Ravenna, Italy, 48121
    • Ospedale S. Maria delle Croci - Ravenna
  • Roma, Italy, 133
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 133
    • Ospedale S. Eugenio
  • Roma, Italy, 133
    • Policlinico Tor Vergata
  • Roma, Italy, 20132
    • Irccs Ospedale San Raffaele
  • Roma, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Roma, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara
  • Roma, Italy, 80131
    • Azienda Ospedaliera Universitaria "Federico II"
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
  • Salerno, Italy, 84131
    • Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
  • Torino, Italy, 10128
    • Azienda Ospedaliera Ordine Mauriziano di Torino
  • Torino, Italy, 10126
    • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette
  • Varese, Italy, 21100
    • ASST dei Sette Laghi - Ospedale di Circolo e Fondazione Macchi Varese
• Japan
  • Akita, Japan, 010-8543
    • Akita University Hospital
  • Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Chiba, Japan, 260-0852
    • Chiba Aoba Municipal Hospital
  • Chiba, Japan, 296-0041
    • Kameda Medical Center - Kameda General Hospital
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Gifu, Japan, 500-8513
    • Gifu Municipal Hospital
  • Kagoshima, Japan, 892-0853
    • National Hospital Organization Kagoshima Medical Center
  • Kobe, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Tokyo, Japan, 141-8625
    • NTT Medical Center Tokyo
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
    • Toyohashi, Aichi, Japan, 441-8570
      • Toyohashi Municipal Hospital
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0024
      • Ehime Prefectural Central Hospital
  • Fukui
    • Yoshida, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Fukuoka
    • Higashi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Gunma University Hospital
    • Maebashi, Gunma, Japan, 371-0821
      • Gunmaken Saiseikai Maebashi Hospital
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 720-0001
      • Chugoku Central Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0006
      • Sapporo Hokuyu Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
  • Miagi
    • Sendai, Miagi, Japan, 983-8520
      • National Hospital Organization Sendai Medical Center
  • Nara
    • Tenri, Nara, Japan, 632-8552
      • Tenri Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University Hospital
  • Tokyo
    • Bunkyō-Ku, Tokyo, Japan, 113-8677
      • Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
    • Minato-Ku, Tokyo, Japan, 105-0003
      • The Jikei University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Medical Center
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Daegu, Korea, Republic of, 42472
    • Daegu Catholic University Medical Center
  • Hwasun, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Hospital
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital
  • Seoul, Korea, Republic of, 6591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 8308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 4401
    • Soonchunhyang University Seoul Hospital
  • Seoul, Korea, Republic of, 5030
    • Konkuk University Medical Center
  • Sŏwŏn, Korea, Republic of, 16499
    • Ajou University Hospital
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital (UUH)
• Poland
  • Kraków, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie
  • Słupsk, Poland, 76-200
    • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
  • Warszawa, Poland, 00-957
    • Instytut Hematologii i Transfuzjologi
  • Warszawa, Poland, 50367
    • Samodzielny Publiczny Szpital Kliniczny Nr. 1 we Wrocławiu
• Portugal
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra
  • Lisboa, Portugal, 1169050
    • Centro Hospitalar Lisboa Central, EPE - Hospital Santo Antonio dos Capuchos
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João, EPE - Hospital de São João
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António
  • Porto, Portugal, 4200-072
    • Instituto Português Oncologia do Porto Francisco Gentil, EPE
• Romania
  • Bucuresti, Romania, 22328
    • Institutul Clinic Fundeni
  • Bucuresti, Romania, 20125
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 20125
    • Institutul Regional de Oncologie Iasi
  • Bucuresti, Romania, 20125
    • Spitalul Clinic Colțea
  • Bucuresti, Romania, 20125
    • Spitalul Universitar de Urgenta Bucuresti
  • Cluj-Napoca, Romania, 400124
    • Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca
  • Craiova, Romania, 200143
    • Spitalul Clinic Municipal Filantropia Craiova
  • Târgu-Mureş, Romania, 540042
    • Spitalul Clinic Judetean de Urgenta Târgu-Mureş (4005)
  • Târgu-Mureş, Romania, 540136
    • Spitalul Clinic Judetean de Urgenta Târgu-Mureş (4008)
• Russian Federation
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhny Novgorod Regional Clinical Hospital
  • Penza, Russian Federation, 440071
    • Penza Regional Oncology Dispensary
  • Petrozavodsk, Russian Federation, 185019
    • Republican Hospital n.a.V.A. Baranov
  • Ryazan', Russian Federation, 390039
    • Ryazan Regional Clinical Hospital
  • Saint Petersburg, Russian Federation, 197341
    • Almazov Federal North-West Medical Research Centre
  • Saratov, Russian Federation, 410012
    • Saratov State Medical University named after V.I. Razumovsky
  • St. Petersburg, Russian Federation, 191024
    • Russian Research Institute of Hematology and Blood Transfusion
  • St. Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinic and Hospital
  • Tula, Russian Federation, 300053
    • Tula Regional Clinical Hospital
• Serbia
  • Belgrade, Serbia, 11000
    • Klinicki Centar Srbije
  • Nis, Serbia, 18000
    • Klinički Centar Niš
  • Novi Sad, Serbia, 21101
    • Klinicki centar Vojvodine
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital (S) Pte Ltd
  • Singapore, Singapore, 138543
    • Singapore General Hospital
• Spain
  • Albacete, Spain, 2006
    • Complejo Hospitalario Universitario de Albacete - Hospital General Universitario
  • Alicante, Spain, 3010
    • Hospital General Universitario de Alicante
  • Badalona, Spain, 8916
    • Catalan Institute of Oncology (ICO)
  • Barcelona, Spain, 8907
    • Hospital Duran i Reynals
  • Barcelona, Spain, 8003
    • Hospital del Mar
  • Barcelona, Spain, 8036
    • Hospital Clínic i Provincial
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Bilbao, Spain, 48013
    • Hospital de Basurto
  • Cáceres, Spain, 10002
    • Hospital San Pedro de Alcántara
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofía
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Granada, Spain, 18014
    • Complejo Hospitalario Universitario Granada
  • La Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña
  • Las Palmas De Gran Canaria, Spain, 35010
    • Hospital Dr. Negrín
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28223
    • Hospital Quiron Madrid
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga - Hospital General
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturias
  • Pamplona, Spain, 31008
    • Complejo Hospitalario de Navarra
  • Pamplona, Spain, 31008
    • Fundacion Jimenez Diaz
  • Pamplona, Spain, 31008
    • Hospital Clínico Universitario "Lozano Blesa"
  • Pamplona, Spain, 31008
    • Hospital General Universitario Morales Meseguer
  • Pamplona, Spain, 31008
    • Hospital Universitario Miguel Servet
  • Pamplona, Spain, 31008
    • Hospital Alvaro Cunqueiro
  • Salamanca, Spain, 37007
    • Hosp Universitario Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Santiago de Compostela, Spain, 15706
    • Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Tarragona, Spain, 43005
    • Hospital Universitari Joan Xxiii de Tarragona
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Valencia, Spain, CP 46026
    • Hospital Universitari i Politecnic La Fe
  • Mallorca
    • Palma, Mallorca, Spain, 7014
      • Hospital Universitari Son Espases
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Medical Foundation - Linkou Branch
  • Niaosong District
    • Kaohsiung, Niaosong District, Taiwan, 83301
      • Chang Gung Medical Foundation - Kaohsiung Branch
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Cherkasy Regional Oncology Dispensary
  • Poltava, Ukraine, 36011
    • Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho
  • Vinnytsia, Ukraine, 21018
    • Vinnitsa Regional Clinical Hospital im. N.I. Pirogov
  • Zhytomyr, Ukraine, 10002
    • Zhitomir Regional Clinical Hospital
• United Kingdom
  • Maidstone, United Kingdom, ME16 9QQ
    • Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 90095
      • University of Florida (UF) Health Shands Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health Indianapolis
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Chandler Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • Valhalla, New York, United States, 10595
      • NY Medical College - Hudson Valley Hematology Oncology Associates
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clinical Research Institute
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Seidman Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospitals, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy plus quizartinib; Induction: up to 2 cycles with cytarabine and daunorubicin/idarubicin, followed by the experimental drug quizartinib Consolidation: up to 4 cycles of cytarabine followed by the experimental drug quizartinib and/or hematopoeitic stem cell transplant Continuation: up to 36 cycles with the experimental drug quizartinib	Drug: Chemotherapy; Other Names: Cytarabine; Daunorubicin; Idarubicin; Drug: Quizartinib; Other Names: Test Product
Active Comparator: Chemotherapy plus placebo; Induction: up to 2 cycles with cytarabine and daunorubicin/idarubicin, followed by placebo Consolidation: up to 4 cycles of cytarabine followed by placebo and/or hematopoeitic stem cell transplant Continuation: up to 36 cycles with placebo	Drug: Placebo; Other Names: Placebo Control; Drug: Chemotherapy; Other Names: Cytarabine; Daunorubicin; Idarubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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)
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)
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 <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts], 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)
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 <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts], 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)
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 <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts]. 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)
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 <5% blasts, >1000 neutrophils, >100,000 platelets, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts], 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)
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State	AUCss was assessed by population Pharmacokinetic (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)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Publications and helpful links

General Publications

• Cortes J, Perl AE, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Kramer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. doi: 10.1016/S1470-2045(18)30240-7. Epub 2018 May 31.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): August 13, 2021
• Study Completion (Actual): June 16, 2023

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: January 28, 2016
• First Posted (Estimated): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Consolidation chemotherapy; AML; Chemotherapy; FLT3-ITD; Quizartinib; Induction chemotherapy; AC220; Newly diagnosed Acute Myeloid Leukemia; FLT3-ITD positive; Feline McDonough sarcoma (FMS)-like tyrosine kinase 3
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Tyrosine Kinase Inhibitors; Cytarabine; Daunorubicin; Idarubicin; Quizartinib
• Other Study ID Numbers: AC220-A-U302; 2015-004856-24 (EudraCT Number); 173667 (Registry Identifier: JAPIC CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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