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

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02668653

Collaborator

(none)

539

Enrollment

244

Locations

Arms

Anticipated Duration (Months)

2.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Leukemia	Drug: Chemotherapy Drug: Quizartinib Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

539 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Aug 13, 2021

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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: Chemotherapy Other Names: Cytarabine Daunorubicin Idarubicin Drug: Placebo Other Names: Placebo Control

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: Chemotherapy

Other Names:

Cytarabine

Daunorubicin

Idarubicin

Drug: Placebo

Other Names:

Placebo Control

Outcome Measures

Primary Outcome Measures

Overall Survival [Approximately 3 years after enrollment]

Secondary Outcome Measures

Event-free Survival [Approximately 3 years after enrollment]
Complete Remission (CR) Rate at the End of Induction [Approximately 21 days up to 120 days]
Composite CR Rate at the End of Induction [Approximately 21 days up to 120 days]
Percentage of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity [Approximately 21 days up to 120 days]
Percentage of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity [Approximately 21 days up to 120 days]
Percentage of Participants with Treatment-emergent Adverse Events [Baseline up to 30 days after last dose, up to 42 cycles (each cycle is 28 days)]
Pharmacokinetic Summary of Area Under the Concentration Versus Time Curve From The Time 0 to 24 Hours (AUC0-24) During the Induction Phase [Cycle 1: Day 8, predose, 1, 2, 4, 6 hours postdose; Day 9, 24 hours postdose; Day 21, predose, 1, 2, 4, 6 hours postdose; Day 22, 24 hours postdose (each cycle is 28 days)]
Pharmacokinetic (PK) samples will be collected on the day and timepoint in hours (h) specified. AUC0-24 will be assessed for quizartinib and active metabolite AC886.
Pharmacokinetic Summary of Maximum Plasma Concentration (Cmax) During the Induction Phase [Cycle 1: Day 8, predose, 1, 2, 4, 6 hours postdose; Day 9, 24 hours postdose; Day 21, predose, 1, 2, 4, 6 hours postdose; Day 22, 24 hours postdose (each cycle is 28 days)]
Pharmacokinetic (PK) samples will be collected on the day and timepoint in hours (h) specified. Cmax will be assessed for quizartinib and active metabolite AC886.
Pharmacokinetic Summary of Minimum Plasma Concentration (Cmin) During the Induction Phase [Cycle 1: Day 8, predose, 1, 2, 4, 6 hours postdose; Day 9, 24 hours postdose; Day 21, predose, 1, 2, 4, 6 hours postdose; Day 22, 24 hours postdose (each cycle is 28 days)]
Pharmacokinetic (PK) samples will be collected on the day and timepoint in hours (h) specified. Cmin will be assessed for quizartinib and active metabolite AC886.
Pharmacokinetic Summary of Time to Maximum Plasma Concentration (Tmax) During the Induction Phase [Cycle 1: Day 8, predose, 1, 2, 4, 6 hours postdose; Day 9, 24 hours postdose; Day 21, predose, 1, 2, 4, 6 hours postdose; Day 22, 24 hours postdose (each cycle is 28 days)]
Pharmacokinetic (PK) samples will be collected on the day and timepoint in hours (h) specified. Tmax will be assessed for quizartinib and active metabolite AC886.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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;
Is ≥18 years or the minimum legal adult age (whichever is greater) and ≤75 years (at Screening);
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);
Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (at the time the participant signs their first ICF);
Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ≥3% FLT3-ITD/total FLT3);
Participant is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol;
Adequate renal function defined as:

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

Adequate hepatic function defined as:
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;
Serum alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN;
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;
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);
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:

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

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

Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;
Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C);
Known history of human immunodeficiency virus (HIV). Participants should be tested for HIV prior to Randomization if required by local regulations or EC;
History of hypersensitivity to any excipients in the quizartinib/placebo tablets;
Females who are pregnant or breastfeeding;
Otherwise considered inappropriate for the study by the Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida (UF) Health Shands Hospital	Gainesville	Florida	United States	90095-7170
2	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
3	Franciscan St. Francis Health Indianapolis	Indianapolis	Indiana	United States	46237
4	University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
5	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
6	NY Medical College - Hudson Valley Hematology Oncology Associates	Valhalla	New York	United States	10595
7	Duke Clinical Research Institute	Durham	North Carolina	United States	27710
8	University Hospitals Seidman Cancer Center	Cleveland	Ohio	United States	44106
9	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107-4307
11	West Virginia University Hospitals, Inc.	Morgantown	West Virginia	United States	26506
12	Sanatorio Britanico	Rosario	Santa Fe	Argentina	S2000CVB
13	Sanatorio Allende	Córdoba		Argentina	X5000JHQ
14	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
15	Townsville Hospital (TTH)	Douglas	Queensland	Australia	4814
16	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
17	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
18	AZ Sint-Jan Brugge-Oostende AV	Brugge		Belgium	8000
19	Universitair Ziekenhuis Gent	Gent		Belgium	9000
20	UCL Mont-Godinne	Yvoir		Belgium	5530
21	Hospital Amaral Carvalho	Brasília		Brazil	70750-521
22	Hospital do CEPON	Brasília		Brazil	70750-521
23	Instituto do Cancer do Estado de São Paulo	Brasília		Brazil	70750-521
24	Santa Casa de Misericórdia de Porto Alegre	Brasília		Brazil	70750-521
25	Hospital da Cidade de Passo Fundo	Passo Fundo		Brazil	99010-260
26	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil	90035-903
27	University Multiprofile Hospital for Active Treatment "Dr. G. Stranski" EAD	Pleven		Bulgaria	5800
28	University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD	Sofia		Bulgaria	1000
29	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
30	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G-3G3
31	Vancouver General Hospital (VGH)	Vancouver	British Columbia	Canada	V5Z 1M9
32	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 1X5
33	Peking University First Hospital	Beijing		China	100034
34	The General Hospital of People's Liberation Army (301 Hospital)	Beijing		China	100853
35	Fujian Medical University Union Hospital	Fuzhou		China	350001
36	Guangdong General Hospital	Guangzhou		China	510030
37	Lanzhou University Second Hospital	Lanzhou		China	730030
38	Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School	Shanghai		China	200025
39	West China Hospital, Sichuan University	Taiyuan		China	30001
40	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin		China	300020
41	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou		China	325015
42	Tang Du Hospital, Fourth Military Medical University	Xi'an		China	710038
43	Henan Cancer Hospital	Zhengzhou		China	450008
44	Klinička Bolnica Dubrava	Zagreb		Croatia	10000
45	Klinička Bolnica Merkur	Zagreb		Croatia	10000
46	Klinički Bolnički Centar Zagreb	Zagreb		Croatia	10000
47	Fakultní Nemocnice Hradec Králové	Hradec Kralove		Czechia	500 05
48	Fakultní Nemocnice Olomouc	Olomouc		Czechia	775 20
49	Fakultní Nemocnice Ostrava	Ostrava		Czechia	708 52
50	Fakultni Nemocnice Plzen	Plzen		Czechia	304 60
51	Vseobecna Fakultni Nemocnice, Ustav hematologie a krevni transfuze (UHKT)	Praha 2		Czechia	128 20
52	Hospital A. Michallon	Grenoble		France	38043
53	Centre Hospitalier de Versailles - Hôpital André Mignot	Le Chesnay		France	78150
54	Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez	Lille		France	59037
55	Centre Léon Bérard	Lyon		France	69373
56	L'Institut Paoli - Calmettes	Marguerittes		France	13009
57	Hôpital de la Conception	Marseille		France	13385
58	CHRU Montpellier - Saint Eloi	Montpellier		France	34295
59	Hôpital Saint-Antoine	Paris		France	75012
60	Hôpital Saint-Louis	Paris		France	75475
61	Hôpital Haut-Lévêque	Pessac		France	33604
62	Centre Hospitalier Lyon-Sud	Pierre Benite		France	69495
63	Centre Henri Becquerel - Centre de Lutte Contre le Cancer	Rouen		France	76038
64	Centre Hospitalier Universitaire de Toulouse - Hôpital Purpan	Toulouse		France	31059
65	HELIOS Klinikum Bad Saarow	Bad Saarow		Germany	15526
66	Charité - Universitätsmedizin Berlin	Berlin		Germany	10117
67	Städtisches Klinikum Braunschweig gGmbH	Braunschweig		Germany	38114
68	Marien Hospital Düsseldorf GmbH	Düsseldorf		Germany	40479
69	Universitätsklinikum Essen	Essen		Germany	45122
70	Universitätsklinikum Frankfurt	Frankfurt am Main		Germany	60590
71	Universitätsklinikum Halle (Saale)	Halle		Germany	6120
72	Evangelisches Krankenhaus Hamm gGmbH	Hamm		Germany	59063
73	Medizinische Hochschule Hannover (MHH)	Hannöver		Germany	30625
74	Universitätsklinikum Münster	Heidelberg		Germany	69115
75	Universitätsklinikum Tübingen	Heidelberg		Germany	69115
76	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
77	Universitätsklinikum Leipzig	Leipzig		Germany	4103
78	Stauferklinikum Schwäbisch Gmünd	Mutlangen		Germany	73557
79	HELIOS Klinikum Wuppertal	Wuppertal		Germany	42283
80	Prince of Wales Hospital	Shatin		Hong Kong
81	Markusovszky Egyetemi Oktatókórház	Budapest		Hungary	1051
82	Szegedi Tudományegyetem	Budapest		Hungary	1051
83	Semmelweis Egyetem	Budapest		Hungary	1083
84	Debreceni Egyetem Klinikai Központ	Debrecen		Hungary	4032
85	Pecsi Tudomanyegyetem Klinikai Központ	Pécs		Hungary	7624
86	Markusovszky Egyetemi Oktatókórház	Szombathely		Hungary	9700
87	Assaf Harofeh Medical Center	Be'er Ya'aqov	Tsifrin	Israel	70300
88	Bnai Zion Medical Center	Haifa		Israel	31048
89	Rambam Medical Center	Haifa		Israel	31096
90	Hadassah University Medical Center	Jerusalem		Israel	91120
91	Rabin Medical Center - Beilinson Hospital	Petaẖ Tiqwa		Israel	49100
92	The Chaim Sheba Medical Center	Ramat-Gan		Israel	52621
93	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
94	Azienda Ospedaliera Nazionale SS.Antonio e Biagio e Cesare Arrigo	Alessandria		Italy	15121
95	Azienda Sanitaria Locale 13 - Ospedale "C. e G. Mazzoni"- Ascoli Piceno	Ascoli Piceno		Italy	63100
96	Azienda Ospedaliero - Universitaria Consorziale Policlinico di Bari	Bari		Italy	70124
97	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna		Italy	40138
98	IRCCS AOU San Martino - IST	Genova		Italy	16132
99	ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
100	A.O.R.N. "A. Cardarelli"	Napoli		Italy	80131
101	Azienda Ospedaliero Universitaria Maggiore della Carità di Novara	Novara		Italy	28100
102	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano		Italy	10043
103	Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello	Palermo		Italy	90146
104	Ospedale S. Maria delle Croci - Ravenna	Ravenna		Italy	48121
105	Fondazione Policlinico Universitario Agostino Gemelli	Roma		Italy	133
106	Ospedale S. Eugenio	Roma		Italy	133
107	Policlinico Tor Vergata	Roma		Italy	133
108	IRCCS Ospedale San Raffaele	Roma		Italy	20132
109	Azienda Ospedaliero-Universitaria Careggi	Roma		Italy	50134
110	Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara	Roma		Italy	56126
111	Azienda Ospedaliera Universitaria "Federico II"	Roma		Italy	80131
112	Istituto Clinico Humanitas	Rozzano		Italy	20089
113	Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi d'Aragona	Salerno		Italy	84131
114	Azienda Ospedaliera Universitaria Senese	Siena		Italy	53100
115	Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette	Torino		Italy	10126
116	Azienda Ospedaliera Ordine Mauriziano di Torino	Torino		Italy	10128
117	ASST dei Sette Laghi - Ospedale di Circolo e Fondazione Macchi Varese	Varese		Italy	21100
118	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi	Japan	460-0001
119	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
120	Toyohashi Municipal Hospital	Toyohashi	Aichi	Japan	441-8570
121	Ehime Prefectural Central Hospital	Matsuyama	Ehime	Japan	790-0024
122	University of Fukui Hospital	Yoshida	Fukui	Japan	910-1193
123	Kyushu University Hospital	Higashi	Fukuoka	Japan	812-8582
124	Gunmaken Saiseikai Maebashi Hospital	Maebashi	Gunma	Japan	371-0821
125	Gunma University Hospital	Maebashi	Gunma	Japan	371-8511
126	Chugoku Central Hospital	Fukuyama	Hiroshima	Japan	720-0001
127	Sapporo Hokuyu Hospital	Sapporo	Hokkaido	Japan	003-0006
128	Yokohama City University Hospital	Yokohama	Kanagawa	Japan	236-0004
129	National Hospital Organization Sendai Medical Center	Sendai	Miagi	Japan	983-8520
130	Tenri Hospital	Tenri	Nara	Japan	632-8552
131	Hamamatsu University Hospital	Hamamatsu	Shizuoka	Japan	431-3192
132	Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital	Bunkyō-Ku	Tokyo	Japan	113-8677
133	The Jikei University Hospital	Minato-Ku	Tokyo	Japan	105-0003
134	Akita University Hospital	Akita		Japan	010-8543
135	Aomori Prefectural Central Hospital	Aomori		Japan	030-8553
136	Chiba Aoba Municipal Hospital	Chiba		Japan	260-0852
137	Kameda Medical Center - Kameda General Hospital	Chiba		Japan	296-0041
138	National Hospital Organization Kyushu Cancer Center	Fukuoka		Japan	811-1395
139	Gifu Municipal Hospital	Gifu		Japan	500-8513
140	National Hospital Organization Kagoshima Medical Center	Kagoshima		Japan	892-0853
141	Kobe City Medical Center General Hospital	Kobe		Japan	650-0047
142	National Hospital Organization Kumamoto Medical Center	Kumamoto		Japan	860-0008
143	Nagasaki University Hospital	Nagasaki		Japan	852-8501
144	Osaka City General Hospital	Osaka		Japan	534-0021
145	Osaka Red Cross Hospital	Osaka		Japan	543-8555
146	NTT Medical Center Tokyo	Tokyo		Japan	141-8625
147	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
148	Pusan National University Hospital	Busan		Korea, Republic of	49241
149	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
150	Yeungnam University Medical Center	Daegu		Korea, Republic of	42415
151	Daegu Catholic University Medical Center	Daegu		Korea, Republic of	42472
152	Chonnam National University Hwasun Hospital	Hwasun		Korea, Republic of	58128
153	Gachon University Gil Hospital	Incheon		Korea, Republic of	21565
154	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13620
155	Seoul National University Hospital	Seoul		Korea, Republic of	3080
156	Severance Hospital	Seoul		Korea, Republic of	3722
157	SoonChunHyang University Seoul Hospital	Seoul		Korea, Republic of	4401
158	Konkuk University Medical Center	Seoul		Korea, Republic of	5030
159	Asan Medical Center	Seoul		Korea, Republic of	5505
160	Samsung Medical Center	Seoul		Korea, Republic of	6351
161	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	6591
162	Korea University Guro Hospital	Seoul		Korea, Republic of	8308
163	Ajou University Hospital	Sŏwŏn		Korea, Republic of	16499
164	Ulsan University Hospital (UUH)	Ulsan		Korea, Republic of	44033
165	Szpital Uniwersytecki w Krakowie	Kraków		Poland	31-501
166	Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka	Słupsk		Poland	76-200
167	Instytut Hematologii i Transfuzjologi	Warszawa		Poland	00-957
168	Samodzielny Publiczny Szpital Kliniczny Nr. 1 we Wrocławiu	Warszawa		Poland	50367
169	Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra	Coimbra		Portugal	3000-075
170	Centro Hospitalar Lisboa Central, EPE - Hospital Santo António dos Capuchos	Lisboa		Portugal	1169050
171	Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António	Porto		Portugal	4099-001
172	Instituto Português Oncologia do Porto Francisco Gentil, EPE	Porto		Portugal	4200-072
173	Centro Hospitalar de São João, EPE - Hospital de São João	Porto		Portugal	4200-319
174	Institutul Regional de Oncologie Iași	Bucuresti		Romania	20125
175	Spitalul Clinic Colentina	Bucuresti		Romania	20125
176	Spitalul Clinic Coltea	Bucuresti		Romania	20125
177	Spitalul Universitar de Urgenta Bucuresti	Bucuresti		Romania	20125
178	Institutul Clinic Fundeni	Bucuresti		Romania	22328
179	Institutul Oncologic "Prof. Dr. Ion Chiricuţă" Cluj Napoca	Cluj-Napoca		Romania	400124
180	Spitalul Clinic Municipal Filantropia Craiova	Craiova		Romania	200143
181	Spitalul Clinic Judetean de Urgenta Târgu-Mureş (4005)	Târgu-Mureş		Romania	540042
182	Spitalul Clinic Judetean de Urgenta Târgu-Mureş (4008)	Târgu-Mureş		Romania	540136
183	Nizhny Novgorod Regional Clinical Hospital	Nizhny Novgorod		Russian Federation	603126
184	Penza Regional Oncology Dispensary	Penza		Russian Federation	440071
185	Republican Hospital n.a.V.A. Baranov	Petrozavodsk		Russian Federation	185019
186	Ryazan Regional Clinical Hospital	Ryazan'		Russian Federation	390039
187	Almazov Federal North-West Medical Research Centre	Saint Petersburg		Russian Federation	197341
188	Saratov State Medical University named after V.I. Razumovsky	Saratov		Russian Federation	410012
189	Russian Research Institute of Hematology and Blood Transfusion	St. Petersburg		Russian Federation	191024
190	Leningrad Regional Clinic and Hospital	St. Petersburg		Russian Federation	194291
191	Tula Regional Clinical Hospital	Tula		Russian Federation	300053
192	Klinički Centar Srbije	Belgrade		Serbia	11000
193	Klinički Centar Niš	Nis		Serbia	18000
194	Klinički Centar Vojvodine	Novi Sad		Serbia	21101
195	National University Hospital (S) Pte Ltd	Singapore		Singapore	119074
196	Singapore General Hospital	Singapore		Singapore	138543
197	Hospital Universitari Son Espases	Palma	Mallorca	Spain	7014
198	Complejo Hospitalario Universitario de Albacete - Hospital General Universitario	Albacete		Spain	2006
199	Hospital General Universitario de Alicante	Alicante		Spain	3010
200	Catalan Institute of Oncology (ICO)	Badalona		Spain	8916
201	Hospital del Mar	Barcelona		Spain	8003
202	Hospital Universitario Vall d'Hebron	Barcelona		Spain	8035
203	Hospital Clinic i Provincial	Barcelona		Spain	8036
204	Hospital Duran i Reynals	Barcelona		Spain	8907
205	Hospital de Basurto	Bilbao		Spain	48013
206	Hospital San Pedro de Alcántara	Cáceres		Spain	10002
207	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
208	Hospital Universitari de Girona Doctor Josep Trueta	Girona		Spain	17007
209	Complejo Hospitalario Universitario Granada	Granada		Spain	18014
210	Complexo Hospitalario Universitario A Coruña	La Coruña		Spain	15006
211	Hospital Dr. Negrín	Las Palmas De Gran Canaria		Spain	35010
212	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
213	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
214	Hospital Clínico San Carlos	Madrid		Spain	28040
215	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
216	Hospital Quirón Madrid	Madrid		Spain	28223
217	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda		Spain	28222
218	Hospital Regional Universitario de Málaga - Hospital General	Málaga		Spain	29010
219	Hospital Universitario Central de Asturias	Oviedo		Spain	33011
220	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
221	Fundación Jiménez Díaz	Pamplona		Spain	31008
222	Hospital Clínico Universitario "Lozano Blesa"	Pamplona		Spain	31008
223	Hospital General Universitario Morales Meseguer	Pamplona		Spain	31008
224	Hospital Universitario Miguel Servet	Pamplona		Spain	31008
225	Hospital Álvaro Cunqueiro	Pamplona		Spain	31008
226	Hosp Universitario Salamanca	Salamanca		Spain	37007
227	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
228	Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario	Santiago de Compostela		Spain	15706
229	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
230	Hospital Universitari Joan XXIII de Tarragona	Tarragona		Spain	43005
231	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
232	Hospital Universitario Dr. Peset	Valencia		Spain	46017
233	Hospital Universitari i Politècnic La Fe	Valencia		Spain	CP 46026
234	Chang Gung Medical Foundation - Kaohsiung Branch	Kaohsiung	Niaosong District	Taiwan	83301
235	China Medical University Hospital	Taichung		Taiwan	40447
236	National Cheng Kung University Hospital	Tainan		Taiwan	704
237	National Taiwan University Hospital	Taipei		Taiwan	100
238	Taipei Veterans General Hospital	Taipei		Taiwan	11217
239	Chang Gung Medical Foundation - Linkou Branch	Taoyuan		Taiwan	33305
240	Cherkasy Regional Oncology Dispensary	Cherkasy		Ukraine	18009
241	Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho	Poltava		Ukraine	36011
242	Vinnitsa Regional Clinical Hospital im. N.I. Pirogov	Vinnytsia		Ukraine	21018
243	Zhitomir Regional Clinical Hospital	Zhytomyr		Ukraine	10002
244	Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital	Maidstone		United Kingdom	ME16 9QQ