TRANSFORM-2: Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis

Sponsor

AbbVie (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04468984

Collaborator

(none)

330

Enrollment

208

Locations

Arms

124.1

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, as compared to best available therapy, for adult participants with MF.

Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. The study has 2 arms - A and B. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. Adult participants with a diagnosis of relapsed/refractory (R/R) MF will be enrolled. Approximately 330 participants will be enrolled in approximately 210 sites across the world.

In Arm A, participants will receive oral navitoclax tablet once daily with oral ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT as identified by the investigator. Treatment will continue until clinical benefit is not seen, participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis (MF)	Drug: Navitoclax Drug: Ruxolitinib Drug: Best Available Therapy (BAT)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

330 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)

Actual Study Start Date :

Aug 31, 2020

Anticipated Primary Completion Date :

Apr 8, 2023

Anticipated Study Completion Date :

Jan 2, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Navitoclax + Ruxolitinib Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.	Drug: Navitoclax Tablet; Oral Other Names: ABT-263 Drug: Ruxolitinib Tablet; Oral
Active Comparator: Arm B: Best Available Therapy (BAT) Participants will receive one of the BAT options, per the investigator's discretion.	Drug: Best Available Therapy (BAT) Tablet/Capsule; Oral or Solution for Subcutaneous Injection

Arm

Intervention/Treatment

Experimental: Arm A: Navitoclax + Ruxolitinib

Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.

Drug: Navitoclax

Tablet; Oral

Other Names:

ABT-263

Drug: Ruxolitinib

Tablet; Oral

Active Comparator: Arm B: Best Available Therapy (BAT)

Participants will receive one of the BAT options, per the investigator's discretion.

Drug: Best Available Therapy (BAT)

Tablet/Capsule; Oral or Solution for Subcutaneous Injection

Outcome Measures

Primary Outcome Measures

Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24) [At Week 24]
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.

Secondary Outcome Measures

Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS) [Baseline (Week 0) Up to Week 24]
Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35) [Baseline (Week 0) Up to Week 97]
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Duration of SVR35 [Baseline (Week 0) Up to Week 97]
Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of disease progression, or to the date of death, whichever occurs first.
Change in Fatigue [Baseline (Week 0) Up to Week 24]
Change in fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a.
Time to Deterioration of Physical Functioning [Baseline (Week 0) Up to Week 97]
Time to deterioration of physical functioning is measured by the physical functioning domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, or death.
Proportion of Participants who achieved Anemia Response [Baseline (Week 0) Up to Week 97]
The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
Overall Survival [Up to approximately 3 years]
Overall survival is defined as the time from start of study to the date of death from any cause.
Leukemia-Free Survival [Up to approximately 3 years]
Leukemia free survival is the time from start of study to the date of development of leukemia.
Overall Response of Clinical Improvement [Baseline (Week 0) Up to Week 97]
Clinical improvement is defined as the achievement of anemia, spleen or symptoms response without progressive disease, per International Working Group (IWG) criteria.
Percentage of Participants who achieve Reduction in Grade of Bone Marrow Fibrosis [Baseline (Week 0) Up to Week 97]
Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be able to complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days prior to randomization.

-- Has at least 2 symptoms with a score >= 3 or a total score of >= 12, as measured by the MFSAF v4.0.

Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF .
Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):
Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.
Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy as defined by any of the following:
Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
A >= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib.
A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of ruxolitinib.
A spleen volume increase of >= 25% (as assessed by Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib.
Prior or current treatment with ruxolitinib for >= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
Baseline platelet count >= 100 × 10^9/L.

Exclusion Criteria:

Received prior treatment with a BH3-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, or prior use of > 1 JAK2 inhibitor or stem cell transplant.
Eligible for allogeneic stem cell transplantation at the time of study entry.
Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 mg daily) and low molecular weight heparin (LMWH).
Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy within 30 days prior to first dose of study drug, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer & Res Ctr /ID# 222162	Chandler	Arizona	United States	85224-5665
2	Highlands Oncology Group Springdale /ID# 221826	Springdale	Arkansas	United States	72762
3	Moores Cancer Center at UC San Diego /ID# 219009	La Jolla	California	United States	92093
4	Long Beach Memorial Medical Ct /ID# 224542	Long Beach	California	United States	90806-1701
5	Icri /Id# 221967	Whittier	California	United States	90603
6	St. Mary's Hospital Regional Cancer Center /ID# 224229	Grand Junction	Colorado	United States	81501-6132
7	Augusta University Georgia Cancer Center /ID# 219051	Augusta	Georgia	United States	30912-0003
8	Columbus Regional Research Institute /ID# 224410	Columbus	Georgia	United States	31904-8915
9	Northwest Oncology & Hematology - Elk Grove Village /ID# 222818	Elk Grove Village	Illinois	United States	60007-3361
10	Loyola University Medical Ctr /ID# 219048	Maywood	Illinois	United States	60153
11	Indiana Blood & Marrow Transpl /ID# 221587	Indianapolis	Indiana	United States	46237
12	Tulane Medical Center - New Orleans /ID# 222940	New Orleans	Louisiana	United States	70112-2600
13	Ochsner Clinic Foundation-New Orleans /ID# 222777	New Orleans	Louisiana	United States	70121
14	American Oncology Partners of Maryland, PA /ID# 222836	Bethesda	Maryland	United States	20817
15	Dana-Farber Cancer Institute /ID# 218998	Boston	Massachusetts	United States	02215
16	University of Michigan /ID# 218463	Ann Arbor	Michigan	United States	48109
17	Henry Ford Health System /ID# 221190	Detroit	Michigan	United States	48202
18	William Beaumont Hospital /ID# 222705	Royal Oak	Michigan	United States	48073-6710
19	Saint Louis University Cancer Center /ID# 222287	Saint Louis	Missouri	United States	63110-2539
20	Summit Medical Group-Florham Park /ID# 222620	Florham Park	New Jersey	United States	07932-1049
21	Hackensack Univ Med Ctr /ID# 219047	Hackensack	New Jersey	United States	07601
22	The Cancer Institute at St. Francis Hospital /ID# 231782	Greenvale	New York	United States	11548-1219
23	Manhattan Hematology Oncology MHO Associates /ID# 223193	New York	New York	United States	10016-6028
24	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 221081	New York	New York	United States	10065-6007
25	Weill Cornell Medical College /ID# 220866	New York	New York	United States	10065
26	Univ Rochester Med Ctr /ID# 219050	Rochester	New York	United States	14642
27	Wake Forest Baptist Medical Center /ID# 222899	Winston-Salem	North Carolina	United States	27157-0001
28	MetroHealth Medical Center /ID# 222650	Cleveland	Ohio	United States	44109
29	Hospital of the University of Pennsylvania /ID# 219001	Philadelphia	Pennsylvania	United States	19104-4238
30	Fox Chase Cancer Center /ID# 223955	Philadelphia	Pennsylvania	United States	19111
31	Houston Methodist Hospital /ID# 223103	Houston	Texas	United States	77030
32	University of Texas Health San Antonio MD Anderson Cancer Center /ID# 233942	San Antonio	Texas	United States	78229
33	Utah Cancer Specialists Salt Lake Clinic /ID# 221962	Salt Lake City	Utah	United States	84106
34	Virginia Cancer Specialists - Fairfax /ID# 223016	Fairfax	Virginia	United States	22031
35	Providence Everett /ID# 223130	Everett	Washington	United States	98201
36	Yakima Valley Memorial Hosp /ID# 224368	Yakima	Washington	United States	98902-6388
37	HSHS St. Vincent Hospital /ID# 224468	Green Bay	Wisconsin	United States	54301
38	The Kinghorn Cancer Centre /ID# 221097	Darlinghurst	New South Wales	Australia	2010
39	Border Medical Oncology Research Unit Albury Wodonga Regional Cancer Centre /ID# 223848	East Albury	New South Wales	Australia	2640
40	Calvary Mater Newcastle /ID# 224324	Waratah	New South Wales	Australia	2298
41	Alfred Health /ID# 221096	Melbourne	Victoria	Australia	3004
42	Royal Perth Hospital /ID# 221099	Perth	Western Australia	Australia	6000
43	Universitaetsklinikum St. Poelten /ID# 221709	Sankt Poelten	Niederoesterreich	Austria	3100
44	Ordensklinikum Linz GmbH Elisabethinen /ID# 220914	Linz	Oberoesterreich	Austria	4010
45	Klinikum Wels-Grieskirchen GmbH /ID# 220915	Wels	Oberoesterreich	Austria	4600
46	Medizinische Universitaet Graz /ID# 220919	Graz	Steiermark	Austria	8036
47	Medizinische Universitaet Wien /ID# 220911	Vienna	Wien	Austria	1090
48	Hanusch Krankenhaus /ID# 220912	Wien		Austria	1140
49	UCL Saint-Luc /ID# 224221	Woluwe-Saint-Lambert	Bruxelles-Capitale	Belgium	1200
50	Grand Hopital de Charleroi /ID# 224827	Charleroi	Hainaut	Belgium	6000
51	UZ Gent /ID# 220841	Gent	Oost-Vlaanderen	Belgium	9000
52	ZNA Stuivenberg /ID# 221468	Antwerp		Belgium	2060
53	AZ-Delta /ID# 221469	Roeselare		Belgium	8800
54	AZ Nikolaas /ID# 228150	Sint-Niklaas		Belgium	9100
55	UMHAT Alexandrovska EAD /ID# 231652	Sofiya	Sofia	Bulgaria	1431
56	UMHAT Dr Georgi Stranski EAD /ID# 231650	Pleven		Bulgaria	5800
57	Acibadem City Clinic Tokuda University Hospital EAD /ID# 231649	Sofia		Bulgaria	1407
58	UMHAT Sveti Ivan Rilski /ID# 231651	Sofia		Bulgaria	1431
59	Juravinski Cancer Centre /ID# 220887	Hamilton	Ontario	Canada	L8V 1C3
60	Ottawa Hospital Research Institute /ID# 238858	Ottawa	Ontario	Canada	K1H 8L6
61	CISSS-CA (Centre Integre de sante et de services sociaux de Chaudiere-Appalache) /ID# 222433	Levis	Quebec	Canada	G6V 3Z1
62	Jewish General Hospital /ID# 243947	Montreal	Quebec	Canada	H3T 1E2
63	McGill University Health Center Research Institute /ID# 222614	Montreal	Quebec	Canada	H4A 3J1
64	Clinical Hospital Dubrava /ID# 230801	Zagreb	Grad Zagreb	Croatia	10000
65	Klinicka bolnica Merkur /ID# 230799	Zagreb	Grad Zagreb	Croatia	10000
66	Klinicki bolnicki centar Zagreb /ID# 230798	Zagreb	Grad Zagreb	Croatia	10000
67	UHC Osijek /ID# 231503	Osijek	Osjecko-baranjska Zupanija	Croatia	31000
68	Klinicki bolnicki centar Split /ID# 230800	Split	Splitsko-dalmatinska Zupanija	Croatia	21000
69	Fakultni Nemocnice Brno /ID# 220959	Brno		Czechia	625 00
70	Vseobecna fakultni nemocnice v Praze /ID# 220969	Praha		Czechia	128 08
71	Aalborg University Hospital /ID# 224391	Aalborg	Nordjylland	Denmark	9000
72	Sjællands Universitetshospital /ID# 224456	Roskilde	Sjælland	Denmark	4000
73	HCL - Hôpital Lyon Sud /ID# 222695	Pierre Benite CEDEX	Auvergne-Rhone-Alpes	France	69495
74	CHU NIMES - Hopital Caremeau /ID# 219128	Nimes CEDEX 9	Gard	France	30029
75	CHU Bordeaux - Hopital Haut Leveque /ID# 222696	Pessac	Gironde	France	33604
76	Hopital Avicenne - APHP /ID# 221287	Bobigny	Ile-de-France	France	93000
77	CHU de Nantes, Hotel Dieu -HME /ID# 219127	Nantes	Pays-de-la-Loire	France	44000
78	Chu Angers /Id# 219129	Angers		France	49933
79	Centre Hospitalier de CHAMBERY /ID# 223771	Chambery		France	73000
80	AP-HP - Hopital Saint-Louis /ID# 221390	Paris		France	75010
81	Universitatsklinikum Mannheim /ID# 221529	Mannheim	Baden-Wuerttemberg	Germany	68167
82	Stauferklinikum Schwaebisch Gmuend /ID# 223948	Mutlangen	Baden-Wuerttemberg	Germany	73557
83	Haematologisch-Onkologische Praxis im Zentrum Augsburg /ID# 225025	Augsburg	Bayern	Germany	86150
84	BAG Freiberg-Richter, Jacobasch, Illmer, Wolf /ID# 221346	Dresden	Sachsen	Germany	01307
85	Augusta-Kranken-Anstalt gGmbH, Bochum-Mitte /ID# 224695	Bochum		Germany	44791
86	Klinikum Chemnitz gGmbH /ID# 224575	Chemnitz		Germany	09116
87	OncoResearch Lerchenfeld GmbH /ID# 225034	Hamburg		Germany	22081
88	Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 221526	Munich		Germany	81675
89	Universitaetsmedizin Rostock /ID# 224157	Rostock		Germany	18057
90	General Hospital of Athens Laiko /ID# 221175	Athens	Attiki	Greece	11527
91	General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 221179	Athens		Greece	10676
92	University General Hospital of Patras /ID# 221178	RION Patras Achaia		Greece	26504
93	General Hospital of Thessaloniki George Papanikolaou /ID# 221463	Thessaloniki		Greece	57010
94	Szegedi Tudomanyegyetem /ID# 220955	Szeged	Csongrad	Hungary	6720
95	Fejer Megyei Szent Gyorgy Korhaz /ID# 220949	Szekesfehervar	Fejer	Hungary	8000
96	Debreceni Egyetem Klinikai Kozpont /ID# 220947	Debrecen	Hajdu-Bihar	Hungary	4032
97	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 220946	Nyíregyháza	Nyiregyhaza	Hungary	4400
98	Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 220948	Kaposvár	Somogy	Hungary	7400
99	The Chaim Sheba Medical Center /ID# 219136	Ramat Gan	Tel-Aviv	Israel	5265601
100	Tel Aviv Sourasky Medical Center /ID# 219135	Tel Aviv-Yafo	Tel-Aviv	Israel	6423906
101	HaEmek Medical Center /ID# 220839	Afula		Israel	1834111
102	Assuta Ashdod Medical Center /ID# 225281	Ashdod		Israel	7747629
103	Assaf Harofeh Medical Center /ID# 222972	Be'Er Ya'Akov		Israel	70300
104	Rambam Health Care Campus /ID# 219121	Haifa		Israel	3109601
105	The Lady Davis Carmel Medical Center /ID# 222973	Haifa		Israel	34362
106	Hadassah Medical Center-Hebrew University /ID# 219111	Jerusalem		Israel	91120
107	Galilee Medical Center /ID# 225280	Nahariya		Israel	2210001
108	Rabin Medical Center /ID# 219139	Petakh Tikva		Israel	4941492
109	Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 225731	Rome	Lazio	Italy	00161
110	Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 219087	Rome	Lazio	Italy	00168
111	ASST Monza/Ospedale San Gerardo /ID# 225113	Monza	Monza E Brianza	Italy	20900
112	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 238438	Ancona		Italy	60126
113	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 221222	Bergamo		Italy	24127
114	IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 221077	Bologna		Italy	40138
115	A.O.U. Policlinico G. Rodolico S.Marco- Presidio G.Rodolico /ID# 219089	Catania		Italy	95123
116	Azienda Ospedaliero Universitaria Careggi /ID# 219090	Florence		Italy	50134
117	Azienda Ospedaliera Universitaria Federico II /ID# 224673	Napoli		Italy	80131
118	Azienda Ospedaliera Universitaria Paolo Giaccone /ID# 221078	Palermo		Italy	90127
119	Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 221220	Reggio Calabria		Italy	89124
120	A.O.U. Citta della Salute e della Scienza di Torino /ID# 221223	Turin		Italy	10126
121	Azienda Ospedaliera Universitaria Friuli Centrale/Presidio Ospedaliero Universit /ID# 221241	Udine		Italy	33100
122	ASST Sette Laghi /ID# 234183	Varese		Italy	21100
123	Azienda ULSS 8 Berica/Ospedale San Bortolo di Vicenza /ID# 221079	Vicenza		Italy	36100
124	Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 221150	Nagoya-shi	Aichi	Japan	453-8511
125	Fujita Health University Hospital /ID# 221598	Toyoake-shi	Aichi	Japan	470-1192
126	Chiba University Hospital /ID# 224546	Chiba-shi	Chiba	Japan	260-8677
127	National Cancer Center Hospital East /ID# 226653	Kashiwa-shi	Chiba	Japan	277-8577
128	Ehime University Hospital /ID# 221158	Toon-shi	Ehime	Japan	791-0295
129	Kyushu University Hospital /ID# 221606	Fukuoka-shi	Fukuoka	Japan	812-8582
130	Fukushima Medical University Hospital /ID# 221877	Fukushima-shi	Fukushima	Japan	960-1295
131	Gifu University Hospital /ID# 224371	Gifu-shi	Gifu	Japan	501-1194
132	Sapporo Hokuyu Hospital /ID# 221149	Sapporo-shi	Hokkaido	Japan	003-0006
133	Kobe City Medical Center General Hospital /ID# 221156	Kobe-shi	Hyogo	Japan	650-0047
134	Kanazawa University Hospital /ID# 223028	Kanazawa-shi	Ishikawa	Japan	920-8641
135	Iwate Medical University Hospital /ID# 222044	Shiwa-gun	Iwate	Japan	028-3695
136	Shonan Kamakura General Hospital /ID# 223030	Kamakura-shi	Kanagawa	Japan	247-8533
137	Kyoto University Hospital /ID# 223008	Kyoto-shi	Kyoto	Japan	606-8507
138	Mie University Hospital /ID# 221665	Tsu-shi	Mie	Japan	514-8507
139	University of Miyazaki Hospital /ID# 221821	Miyazaki-shi	Miyazaki	Japan	889-1692
140	Niigata University Medical & Dental Hospital /ID# 223034	Niigata-shi	Niigata	Japan	951-8520
141	Kurashiki Central Hospital /ID# 221690	Kurashiki-shi	Okayama	Japan	710-8602
142	Osaka University Hospital /ID# 221159	Suita-shi	Osaka	Japan	565-0871
143	Dokkyo Medical University Saitama Medical Center /ID# 222334	Koshigaya-shi	Saitama	Japan	343-8555
144	Juntendo University Shizuoka Hospital /ID# 221780	Izunokuni-shi	Shizuoka	Japan	410-2295
145	Juntendo University Hospital /ID# 221154	Bunkyo-ku	Tokyo	Japan	113-8431
146	Nippon Medical School Hospital /ID# 221676	Bunkyo-ku	Tokyo	Japan	113-8602
147	Tokyo Medical University Hospital /ID# 221540	Shinjuku-ku	Tokyo	Japan	160-0023
148	University of Yamanashi Hospital /ID# 221706	Chuo-shi	Yamanashi	Japan	409-3821
149	Pusan National University Hospital /ID# 220980	Busan		Korea, Republic of	49241
150	Gachon University Gil Medical Center /ID# 220972	Incheon		Korea, Republic of	21565
151	Seoul National University Hospital /ID# 219060	Seoul		Korea, Republic of	03080
152	Samsung Medical Center /ID# 221091	Seoul		Korea, Republic of	06351
153	The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 219061	Seoul		Korea, Republic of	06591
154	Middlemore Clinical Trials /ID# 232201	Papatoetoe	Auckland	New Zealand	2025
155	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 221161	Lodz	Lodzkie	Poland	93-513
156	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 221124	Lublin	Lubelskie	Poland	20-081
157	SP ZOZ Szpital Uniwersytecki w Krakowie /ID# 221160	Krakow	Malopolskie	Poland	31-501
158	LUX MED Onkologia - Szpital Szamocka /ID# 221265	Warszawa	Mazowieckie	Poland	01-748
159	MTZ Clinical Research SP. zoo /ID# 221759	Warszawa	Mazowieckie	Poland	02-106
160	Uniwersyteckie Centrum Kliniczne /ID# 221298	Gdansk	Pomorskie	Poland	80-214
161	ARS-MEDICAL Sp. z o.o. /ID# 238336	Pila	Wielkopolskie	Poland	64-920
162	Pratia Onkologia Katowice /ID# 224526	Katowice		Poland	40-519
163	Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola /ID# 241031	Poznan		Poland	60-569
164	Hospital del Centro Comprensivo de Cancer de la UPR /ID# 223281	San Juan		Puerto Rico	00927
165	Moscow State budget healthcare /ID# 221116	Moscow	Moskva	Russian Federation	125284
166	Hospital n.a. V.V. Veresaev /ID# 225221	Moscow		Russian Federation	127644
167	Russian Research Institute of Hematology and Transfusiology of the FMBA /ID# 221115	Sankt-Peterburg		Russian Federation	191024
168	Almazov National Medical Research Centre /ID# 221114	Sankt-Peterburg		Russian Federation	197341
169	Tula Regional Clinical Hospital /ID# 221302	Tula		Russian Federation	300053
170	University Clinical Center Serbia /ID# 231058	Belgrade	Beograd	Serbia	11000
171	Clin Hosp Ctr Bezanijska Kosa /ID# 231059	Belgrade	Beograd	Serbia	11080
172	Clinical Center Vojvodina /ID# 231057	Novi Sad	Vojvodina	Serbia	21000
173	Wits Clinical Research Site /ID# 231554	Johannesburg	Gauteng	South Africa	2193
174	Albert Alberts Stem Cell Transplant Centre /ID# 231556	Pretoria	Gauteng	South Africa	0044
175	Hospital Clínico Universitario de Santiago-CHUS /ID# 221616	Santiago de Compostela	A Coruna	Spain	15706
176	Hospital Universitario Central de Asturias /ID# 224815	Oviedo	Asturias	Spain	33011
177	Hospital Universitario Germans Trias i Pujol /ID# 233727	Badalona	Barcelona	Spain	08916
178	Hospital Universitario Dr. Negrin /ID# 220923	Las Palmas de Gran Canaria	Las Palmas	Spain	35019
179	Hospital Regional de Malaga /ID# 221906	Málaga	Malaga	Spain	29010
180	Hospital Universitario A Coruna - CHUAC /ID# 224617	A Coruna		Spain	15006
181	Hospital Parc de Salut del Mar /ID# 220922	Barcelona		Spain	08003
182	Hospital Universitario Vall d'Hebron /ID# 240979	Barcelona		Spain	08035
183	Hospital Universitario 12 de Octubre /ID# 233726	Madrid		Spain	28041
184	Hospital Universitario La Paz /ID# 224813	Madrid		Spain	28046
185	Hospital Universitario de Salamanca /ID# 221904	Salamanca		Spain	37711
186	Hospital Universitario Virgen del Rocio /ID# 221932	Sevilla		Spain	41013
187	Hospital Clinico Universitario de Valencia /ID# 220920	Valencia		Spain	46010
188	Skane University Hospital Lund /ID# 220834	Lund	Skane Lan	Sweden	SE 221 41
189	Universitätsspital Basel /ID# 221261	Basel	Basel-Stadt	Switzerland	4031
190	Inselspital, Universitätsspital Bern /ID# 223439	Bern		Switzerland	3010
191	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 218980	Kaohsiung		Taiwan	807
192	Kaohsiung Chang Gung Memorial Hospital /ID# 218985	Kaohsiung		Taiwan	833
193	China Medical University Hospital /ID# 218979	Taichung City		Taiwan	40447
194	Chi Mei Hospital - Liouying /ID# 221144	Tainan City		Taiwan	73657
195	Taipei Veterans General Hosp /ID# 221147	Taipei City		Taiwan	11217
196	Linkou Chang Gung Memorial Hospital /ID# 218982	Taoyuan City		Taiwan	333
197	Gulhane Askeri Tip Academy /ID# 224568	Ankara		Turkey	06010
198	Trakya University Medical Facu /ID# 224572	Edirne, Istanbul		Turkey	22030
199	Ege University Medical Faculty /ID# 224570	Izmir		Turkey	35040
200	Mersin University Medical /ID# 224571	Mersin		Turkey	33343
201	Ondokuz mayis University Facul /ID# 224567	Samsun		Turkey	55200
202	United Lincolnshire Hospitals NHS Trust /ID# 224613	Lincoln	Lincolnshire	United Kingdom	LN2 4AX
203	Guys and St Thomas NHS Foundation Trust /ID# 221041	London	London, City Of	United Kingdom	SE1 9RT
204	James Paget University Hospitals NHS Foundation Trust /ID# 221219	Great Yarmouth	Norfolk	United Kingdom	NR31 6LA
205	Oxford University Hospitals NHS Foundation Trust /ID# 221044	Oxford	Oxfordshire	United Kingdom	OX3 9DU
206	University Hospitals Birmingham NHS Foundation Trust /ID# 221334	Birmingham		United Kingdom	B15 2TH
207	NHS Lothian /ID# 224378	Edinburgh		United Kingdom	EH3 9HE
208	The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 221335	Newcastle Upon Tyne		United Kingdom	NE7 7DN