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

Phase 3

Completed

• Conditions: Acute Myeloid Leukemia; Leukemia
• Interventions: Drug: Chemotherapy; Drug: Placebo; Drug: Quizartinib

• Registration Number: NCT02668653
• Lead Sponsor: Daiichi Sankyo

Brief 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.

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 Timeline

• Study First Submitted: 2016-01-22
• Study First Submitted QC: 2016-01-28
• Study First Posted: 2016-01-29
• Study Start: 2016-09-01
• Primary Completion: 2021-08-13
• Results First Submitted: 2022-08-12
• Results First Submitted QC: 2022-09-27
• Results First Posted: 2022-10-05
• Study Completion: 2023-06-16
• Status Verified: 2024-07
• Last Update Submitted: 2024-08-02
• Last Update Posted: 2024-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 539

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy plus quizartinib	Chemotherapy	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
Chemotherapy plus placebo	Chemotherapy	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
Chemotherapy plus placebo	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
Chemotherapy plus quizartinib	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

Primary Outcome Measures

Name	Time	Method
Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment	Overall survival is defined as the time from randomization until death from any cause.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	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)	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.
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	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)	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.
Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment	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.
Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)	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
Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia	Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)	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.
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max)	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)	Css,max was assessed by population PK analysis during Cycle 1 of each phase.
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss)	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)	Tmax,ss was assessed by population PK analysis during Cycle 1 of each phase.
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	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)	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.
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State	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)	AUCss was assessed by population Pharmacokinetic (PK) analysis during Cycle 1 of each phase.

Trial Locations

Locations (243)

University Hospitals Seidman Cancer Center; 🇺🇸 Cleveland, Ohio, United States

University of Florida (UF) Health Shands Hospital; 🇺🇸 Gainesville, Florida, United States

The University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

NY Medical College - Hudson Valley Hematology Oncology Associates; 🇺🇸 Valhalla, New York, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

West Virginia University Hospitals, Inc.; 🇺🇸 Morgantown, West Virginia, United States

Sanatorio Britanico; 🇦🇷 Rosario, Santa Fe, Argentina

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

AZ Sint-Jan Brugge-Oostende AV; 🇧🇪 Brugge, Belgium

Hospital Amaral Carvalho; 🇧🇷 Brasília, Brazil

Hospital do CEPON; 🇧🇷 Brasília, Brazil

Santa Casa de Misericórdia de Porto Alegre; 🇧🇷 Brasília, Brazil

Instituto do Cancer do Estado de São Paulo; 🇧🇷 Brasília, Brazil

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Hospital da Cidade de Passo Fundo; 🇧🇷 Passo Fundo, Brazil

Vancouver General Hospital (VGH); 🇨🇦 Vancouver, British Columbia, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

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

Lanzhou University Second Hospital; 🇨🇳 Lanzhou, China

Guangdong General Hospital; 🇨🇳 Guangzhou, 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

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China

Tang Du Hospital, Fourth Military Medical University; 🇨🇳 Xi'an, China

Klinička Bolnica Dubrava; 🇭🇷 Zagreb, Croatia

Fakultní Nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

Klinička Bolnica Merkur; 🇭🇷 Zagreb, Croatia

Fakultní Nemocnice Ostrava; 🇨🇿 Ostrava, Czechia

Klinički Bolnički Centar Zagreb; 🇭🇷 Zagreb, Croatia

Fakultní Nemocnice Hradec Králové; 🇨🇿 Hradec Kralove, Czechia

Vseobecna Fakultni Nemocnice, Ustav hematologie a krevni transfuze (UHKT); 🇨🇿 Praha 2, Czechia

Centre Hospitalier de Versailles - Hôpital André Mignot; 🇫🇷 Le Chesnay, France

Hospital A. Michallon; 🇫🇷 Grenoble, France

Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez; 🇫🇷 Lille, France

CHRU Montpellier - Saint Eloi; 🇫🇷 Montpellier, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Hôpital de la Conception; 🇫🇷 Marseille, France

L'Institut Paoli - Calmettes; 🇫🇷 Marguerittes, 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, France

HELIOS Klinikum Bad Saarow; 🇩🇪 Bad Saarow, Germany

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Städtisches Klinikum Braunschweig gGmbH; 🇩🇪 Braunschweig, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt am Main, Germany

Marien Hospital Düsseldorf GmbH; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Universitätsklinikum Halle (Saale); 🇩🇪 Halle, Germany

Evangelisches Krankenhaus Hamm gGmbH; 🇩🇪 Hamm, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Stauferklinikum Schwäbisch Gmünd; 🇩🇪 Mutlangen, Germany

Universitätsklinikum Tübingen; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Münster; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

HELIOS Klinikum Wuppertal; 🇩🇪 Wuppertal, Germany

Markusovszky Egyetemi Oktatókórház; 🇭🇺 Szombathely, Hungary

Prince of Wales Hospital; 🇭🇰 Shatin, Hong Kong

Debreceni Egyetem Klinikai Központ; 🇭🇺 Debrecen, Hungary

Szegedi Tudományegyetem; 🇭🇺 Budapest, Hungary

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

Assaf Harofeh Medical Center; 🇮🇱 Be'er Ya'aqov, Tsifrin, Israel

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

The Chaim Sheba Medical Center; 🇮🇱 Ramat-Gan, Israel

Rambam Medical Center; 🇮🇱 Haifa, Israel

Hadassah University Medical Center; 🇮🇱 Jerusalem, Israel

Azienda Sanitaria Locale 13 - Ospedale "C. e G. Mazzoni"- Ascoli Piceno; 🇮🇹 Ascoli Piceno, Italy

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi; 🇮🇹 Bologna, Italy

Azienda Ospedaliero - Universitaria Consorziale Policlinico di Bari; 🇮🇹 Bari, 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

Ospedale S. Maria delle Croci - Ravenna; 🇮🇹 Ravenna, Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello; 🇮🇹 Palermo, Italy

Fondazione Policlinico Universitario Agostino Gemelli; 🇮🇹 Roma, Italy

Ospedale S. Eugenio; 🇮🇹 Roma, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 Roma, Italy

Azienda Ospedaliero-Universitaria Careggi; 🇮🇹 Roma, Italy

Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara; 🇮🇹 Roma, Italy

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy

Azienda Ospedaliera Universitaria "Federico II"; 🇮🇹 Roma, Italy

Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette; 🇮🇹 Torino, 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

ASST dei Sette Laghi - Ospedale di Circolo e Fondazione Macchi Varese; 🇮🇹 Varese, Italy

National Hospital Organization Nagoya Medical Center; 🇯🇵 Nagoya, Aichi, Japan

Toyohashi Municipal Hospital; 🇯🇵 Toyohashi, Aichi, Japan

University of Fukui Hospital; 🇯🇵 Yoshida, Fukui, Japan

Nagoya University Hospital; 🇯🇵 Nagoya, Aichi, Japan

Gunmaken Saiseikai Maebashi Hospital; 🇯🇵 Maebashi, Gunma, Japan

Ehime Prefectural Central Hospital; 🇯🇵 Matsuyama, Ehime, Japan

Kyushu University Hospital; 🇯🇵 Higashi, Fukuoka, Japan

Gunma University Hospital; 🇯🇵 Maebashi, Gunma, Japan

Yokohama City University Hospital; 🇯🇵 Yokohama, Kanagawa, Japan

Chugoku Central Hospital; 🇯🇵 Fukuyama, Hiroshima, Japan

Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital; 🇯🇵 Bunkyō-Ku, Tokyo, Japan

Tenri Hospital; 🇯🇵 Tenri, Nara, Japan

Hamamatsu University Hospital; 🇯🇵 Hamamatsu, Shizuoka, Japan

Inje University Haeundae Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Chiba Aoba Municipal Hospital; 🇯🇵 Chiba, Japan

SoonChunHyang University Seoul Hospital; 🇰🇷 Seoul, Korea, Republic of

Akita University Hospital; 🇯🇵 Akita, Japan

National Hospital Organization Kyushu Cancer Center; 🇯🇵 Fukuoka, Japan

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Aomori Prefectural Central Hospital; 🇯🇵 Aomori, Japan

Kameda Medical Center - Kameda General Hospital; 🇯🇵 Chiba, Japan

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

National Hospital Organization Kagoshima Medical Center; 🇯🇵 Kagoshima, Japan

Gifu Municipal Hospital; 🇯🇵 Gifu, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe, Japan

National Hospital Organization Kumamoto Medical Center; 🇯🇵 Kumamoto, Japan

Nagasaki University Hospital; 🇯🇵 Nagasaki, Japan

Osaka City General Hospital; 🇯🇵 Osaka, Japan

NTT Medical Center Tokyo; 🇯🇵 Tokyo, Japan

Osaka Red Cross Hospital; 🇯🇵 Osaka, Japan

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

Kyungpook National University Hospital; 🇰🇷 Daegu, Korea, Republic of

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun, Korea, Republic of

Yeungnam University Medical Center; 🇰🇷 Daegu, Korea, Republic of

Daegu Catholic University Medical Center; 🇰🇷 Daegu, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Konkuk University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Instytut Hematologii i Transfuzjologi; 🇵🇱 Warszawa, Poland

Szpital Uniwersytecki w Krakowie; 🇵🇱 Kraków, Poland

Ulsan University Hospital (UUH); 🇰🇷 Ulsan, Korea, Republic of

Ajou University Hospital; 🇰🇷 Sŏwŏn, Korea, Republic of

Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka; 🇵🇱 Słupsk, Poland

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

Samodzielny Publiczny Szpital Kliniczny Nr. 1 we Wrocławiu; 🇵🇱 Warszawa, Poland

Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António; 🇵🇹 Porto, Portugal

Instituto Português Oncologia do Porto Francisco Gentil, EPE; 🇵🇹 Porto, Portugal

Spitalul Universitar de Urgenta Bucuresti; 🇷🇴 Bucuresti, Romania

Institutul Clinic Fundeni; 🇷🇴 Bucuresti, Romania

Nizhny Novgorod Regional Clinical Hospital; 🇷🇺 Nizhny Novgorod, Russian Federation

Institutul Oncologic "Prof. Dr. Ion Chiricuţă" Cluj Napoca; 🇷🇴 Cluj-Napoca, Romania

Spitalul Clinic Judetean de Urgenta Târgu-Mureş (4005); 🇷🇴 Târgu-Mureş, Romania

Almazov Federal North-West Medical Research Centre; 🇷🇺 Saint Petersburg, Russian Federation

Penza Regional Oncology Dispensary; 🇷🇺 Penza, Russian Federation

Ryazan Regional Clinical Hospital; 🇷🇺 Ryazan', Russian Federation

Republican Hospital n.a.V.A. Baranov; 🇷🇺 Petrozavodsk, Russian Federation

Tula Regional Clinical Hospital; 🇷🇺 Tula, Russian Federation

Singapore General Hospital; 🇸🇬 Singapore, Singapore

Complejo Hospitalario Universitario de Albacete - Hospital General Universitario; 🇪🇸 Albacete, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Catalan Institute of Oncology (ICO); 🇪🇸 Badalona, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Hospital de Basurto; 🇪🇸 Bilbao, Spain

Complejo Hospitalario Universitario Granada; 🇪🇸 Granada, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Quirón Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Spain

Complejo Hospitalario de Navarra; 🇪🇸 Pamplona, Spain

Fundación Jiménez Díaz; 🇪🇸 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

Hospital Universitario Virgen del Rocío; 🇪🇸 Sevilla, Spain

Hospital Universitari Joan XXIII de Tarragona; 🇪🇸 Tarragona, Spain

Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario; 🇪🇸 Santiago de Compostela, Spain

Hospital Universitario Dr. Peset; 🇪🇸 Valencia, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitari i Politècnic La Fe; 🇪🇸 Valencia, Spain

Chang Gung Medical Foundation - Kaohsiung Branch; 🇨🇳 Kaohsiung, Niaosong District, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

Cherkasy Regional Oncology Dispensary; 🇺🇦 Cherkasy, Ukraine

Chang Gung Medical Foundation - Linkou Branch; 🇨🇳 Taoyuan, Taiwan

Vinnitsa Regional Clinical Hospital im. N.I. Pirogov; 🇺🇦 Vinnytsia, Ukraine

Zhitomir Regional Clinical Hospital; 🇺🇦 Zhytomyr, Ukraine

Russian Research Institute of Hematology and Blood Transfusion; 🇷🇺 St. Petersburg, Russian Federation

Leningrad Regional Clinic and Hospital; 🇷🇺 St. Petersburg, Russian Federation

Saratov State Medical University named after V.I. Razumovsky; 🇷🇺 Saratov, Russian Federation

Hospital Universitari Son Espases; 🇪🇸 Palma, Mallorca, Spain

Hospital General Universitario de Alicante; 🇪🇸 Alicante, Spain

Hospital Clinic i Provincial; 🇪🇸 Barcelona, Spain

Hospital Universitari de Girona Doctor Josep Trueta; 🇪🇸 Girona, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital San Pedro de Alcántara; 🇪🇸 Cáceres, Spain

Complexo Hospitalario Universitario A Coruña; 🇪🇸 La Coruña, Spain

Hospital Universitario Puerta de Hierro - Majadahonda; 🇪🇸 Majadahonda, Spain

Hospital Dr. Negrín; 🇪🇸 Las Palmas De Gran Canaria, Spain

Hospital Regional Universitario de Málaga - Hospital General; 🇪🇸 Málaga, Spain

Hospital Álvaro Cunqueiro; 🇪🇸 Pamplona, Spain

Rabin Medical Center - Beilinson Hospital; 🇮🇱 Petaẖ Tiqwa, Israel

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Pecsi Tudomanyegyetem Klinikai Központ; 🇭🇺 Pécs, Hungary

Fakultni Nemocnice Plzen; 🇨🇿 Plzen, Czechia

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

University of Kentucky Chandler Medical Center; 🇺🇸 Lexington, Kentucky, United States

Duke Clinical Research Institute; 🇺🇸 Durham, North Carolina, United States

Franciscan St. Francis Health Indianapolis; 🇺🇸 Indianapolis, Indiana, United States

John Theurer Cancer Center at Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Sanatorio Allende; 🇦🇷 Córdoba, Argentina

Townsville Hospital (TTH); 🇦🇺 Douglas, Queensland, Australia

UCL Mont-Godinne; 🇧🇪 Yvoir, Belgium

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

University Multiprofile Hospital for Active Treatment "Dr. G. Stranski" EAD; 🇧🇬 Pleven, Bulgaria

University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD; 🇧🇬 Sofia, Bulgaria

Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School; 🇨🇳 Shanghai, China

Medizinische Hochschule Hannover (MHH); 🇩🇪 Hannöver, Germany

Azienda Ospedaliera Nazionale SS.Antonio e Biagio e Cesare Arrigo; 🇮🇹 Alessandria, Italy

Policlinico Tor Vergata; 🇮🇹 Roma, Italy

National Hospital Organization Sendai Medical Center; 🇯🇵 Sendai, Miagi, Japan

Sapporo Hokuyu Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Gachon University Gil Hospital; 🇰🇷 Incheon, Korea, Republic of

The Catholic University of Korea, Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho; 🇺🇦 Poltava, Ukraine

Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital; 🇬🇧 Maidstone, United Kingdom

Spitalul Clinic Coltea; 🇷🇴 Bucuresti, Romania

Spitalul Clinic Judetean de Urgenta Târgu-Mureş (4008); 🇷🇴 Târgu-Mureş, Romania

Klinički Centar Srbije; 🇷🇸 Belgrade, Serbia

Klinički Centar Vojvodine; 🇷🇸 Novi Sad, Serbia

Spitalul Clinic Municipal Filantropia Craiova; 🇷🇴 Craiova, Romania

The Jikei University Hospital; 🇯🇵 Minato-Ku, Tokyo, Japan

Centro Hospitalar de São João, EPE - Hospital de São João; 🇵🇹 Porto, Portugal

Institutul Regional de Oncologie Iași; 🇷🇴 Bucuresti, Romania

Spitalul Clinic Colentina; 🇷🇴 Bucuresti, Romania

Klinički Centar Niš; 🇷🇸 Nis, Serbia

National University Hospital (S) Pte Ltd; 🇸🇬 Singapore, Singapore