OPTIMISMM: Safety and Efficacy of Pomalidomide, Bortezomib and Low-dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT01734928

Collaborator

(none)

559

Enrollment

266

Locations

Arms

112.1

Actual Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of the combination of pomalidomide, bortezomib and low dose dexamethasone to the combination of bortezomib and low dose dexamethasone in participants with relapsed/refractory multiple myeloma. This study will also assess how safe the combination of pomalidomide, bortezomib and low dose dexamethasone is compared to the combination of bortezomib and low dose dexamethasone.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pomalidomide Drug: Bortezomib Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

559 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide, Bortezomib and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Actual Study Start Date :

Jan 7, 2013

Actual Primary Completion Date :

May 9, 2022

Actual Study Completion Date :

May 13, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pomalidomide, Bortezomib and Low Dose Dexamethasone 4 mg of Pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1.3 mg/m2 of Bortezomib administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2,8, 9 of 21 days for cycles 9 and onward until disease progression.	Drug: Pomalidomide Pomalidomide 4 mg will be taken orally on Days 1-14 of a 21-day cycle. Other Names: Oral Pomalidomide CC-4047 Drug: Bortezomib Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression. Other Names: Velcade Drug: Dexamethasone Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [>75 years old] will be taken orally on Days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.
Active Comparator: Bortezomib and Low Dose Dexamethasone 1.3 mg/m2 of Bortezomib will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression along with Dexamethasone 20 mg/day [≤ 75 years old]or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.	Drug: Bortezomib Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression. Other Names: Velcade Drug: Dexamethasone Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [>75 years old] will be taken orally on Days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.

Arm

Intervention/Treatment

Experimental: Pomalidomide, Bortezomib and Low Dose Dexamethasone

4 mg of Pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1.3 mg/m2 of Bortezomib administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2,8, 9 of 21 days for cycles 9 and onward until disease progression.

Drug: Pomalidomide

Pomalidomide 4 mg will be taken orally on Days 1-14 of a 21-day cycle.

Other Names:

Oral Pomalidomide

CC-4047

Drug: Bortezomib

Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression.

Other Names:

Velcade

Drug: Dexamethasone

Dexamethasone 20 mg/day [≤ 75 years old] or 10 mg/day [>75 years old] will be taken orally on Days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.

Active Comparator: Bortezomib and Low Dose Dexamethasone

1.3 mg/m2 of Bortezomib will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression along with Dexamethasone 20 mg/day [≤ 75 years old]or 10 mg/day [> 75 years old] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression.

Drug: Bortezomib

Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression.

Other Names:

Velcade

Drug: Dexamethasone

Outcome Measures

Primary Outcome Measures

Progression Free Survival [Up to 1 year]
The length of time during and after the treatment that participants in the study live without the disease getting worse

Secondary Outcome Measures

Overall Survival [Up to 5 years]
The length of time from start of study treatment that participants in the study are alive
Adverse Event [Up to 1 year]
Number of participants with adverse events
Overall Response Rate [Up to 1 year]
The percentage of participants who respond to study treatment
Duration of Response [Up to 1 year]
The length of time from when participants respond to the study treatment to when their disease gets worse

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be ≥ 18 years at the time of signing informed consent.
Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis.
Must have had at least 1 but no greater than 3 prior anti-myeloma regimens.
Must have documented disease progression during or after their last anti-myeloma therapy.
All subjects must have received prior treatment with a lenalidomide containing regimen for at least 2 consecutive cycles.

Exclusion Criteria:

Documented progressive disease during therapy or within 60 days of the last dose of a bortezomib-containing therapy under the 1.3 mg/m^2 dose twice weekly dosing schedule.
Peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain within 14 days prior to randomization.
Non-secretory multiple myeloma.
Subjects with severe renal impairment requiring dialysis.
Previous therapy with pomalidomide.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Cancer Center	Mobile	Alabama	United States	36608
2	Arizona Oncology	Tucson	Arizona	United States	85710
3	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
4	Alta Bates Comprehensive Cancer Center	Berkeley	California	United States	94704
5	University of California San Francisco Fresno Campus	Fresno	California	United States	93701
6	Marin Oncology Associates	Greenbrae	California	United States	94904-2007
7	Moore UCSD Cancer Center	La Jolla	California	United States	92083
8	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
9	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
10	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
11	Cancer Center of Central Connecticut	Southington	Connecticut	United States	06489
12	George Washington Medical Center	Washington	District of Columbia	United States	20037
13	Lynn Cancer Institute	Boca Raton	Florida	United States	33486
14	University Cancer Institute	Boynton Beach	Florida	United States	33426
15	Broward Oncology Associates PA	Fort Lauderdale	Florida	United States	33308
16	Broward Oncology Assoc.	Fort Lauderdale	Florida	United States	33316
17	University of Florida	Gainesville	Florida	United States	32610
18	Alves Domenech Oncology and Hematology Clinic	Hollywood	Florida	United States	33021
19	Palm Beach Cancer Institute, LLC	West Palm Beach	Florida	United States	33401
20	Local Institution - 135	Marietta	Georgia	United States	30060
21	Northwest Georgia Oncology Centers, PCWilliam S. Gibbons Center Research Institute	Marietta	Georgia	United States	30060
22	University of Chicago	Chicago	Illinois	United States	60637-1470
23	Investigative Clinical Research of Indiana, LLC	Indianapolis	Indiana	United States	46254
24	University of Iowa	Iowa City	Iowa	United States	52242
25	Western Kentucky Hematology and Oncology Group, PSC	Paducah	Kentucky	United States	42003
26	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
27	Cancer Care of Maine	Bangor	Maine	United States	04401
28	Local Institution - 132	Bangor	Maine	United States	04401
29	St. Agnes - Medical Center	Baltimore	Maryland	United States	21229-5299
30	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
31	Local Institution - 125	Bethesda	Maryland	United States	20817
32	Medstar Health Research Institute	Hyattsville	Maryland	United States	20782
33	Local Institution - 299	Boston	Massachusetts	United States	02114
34	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
35	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
36	Local Institution - 100	Boston	Massachusetts	United States	02115
37	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
38	Local Institution - 298	Boston	Massachusetts	United States	02215
39	Henry Ford Medical Center - New Center One	Detroit	Michigan	United States	48202-268
40	Local Institution - 178	Detroit	Michigan	United States	48202-268
41	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan	United States	49546
42	Detroit Clinical Research Center	Lansing	Michigan	United States	48912
43	Beaumont Cancer Center	Royal Oak	Michigan	United States	48073
44	Essentia Health Duluth CCOP	Duluth	Minnesota	United States	55805
45	Metro MN CCOP	Saint Louis Park	Minnesota	United States	55416
46	Columbia Comprehensive	Jefferson City	Missouri	United States	65203
47	Kansas City VA Medical Center University of Kansas Medical Center	Kansas City	Missouri	United States	64128
48	St John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
49	St. John's Clinic Cancerand Hematology - Springfield	Springfield	Missouri	United States	65804
50	Billings Clinic	Billings	Montana	United States	59102
51	Southeast Nebraska Cancer Center	Lincoln	Nebraska	United States	68510
52	CarePoint Health Research Institute	Jersey City	New Jersey	United States	07306
53	Hematology-Oncology Associates of NNJ, P	Morristown	New Jersey	United States	07960
54	Somerset Hematology-Oncology Associates	Somerville	New Jersey	United States	08876
55	Montefiore Medical Center	Bronx	New York	United States	10467
56	Mount Sinai Hospital	New York	New York	United States	10029
57	Stony Brook University	Stony Brook	New York	United States	11794-7300
58	New York Medical College	Valhalla	New York	United States	10595
59	Eastern Institute of Medical Sciences	Greenville	North Carolina	United States	27834
60	Boice-Willis Clinic P.A.	Rocky Mount	North Carolina	United States	27804
61	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
62	Local Institution - 111	Canton	Ohio	United States	44718
63	MetroHealth Medical Systems	Cleveland	Ohio	United States	44109
64	Mid Ohio Oncology Hematology Inc	Columbus	Ohio	United States	43219
65	University of Toledo Medical Center	Toledo	Ohio	United States	43614
66	Providence Portland Medical Center	Portland	Oregon	United States	97213
67	Med Univ of South Carolina	Charleston	South Carolina	United States	29425
68	Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute	Spartanburg	South Carolina	United States	29303
69	Avera Research Institute	Sioux Falls	South Dakota	United States	57105
70	Local Institution - 167	Watertown	South Dakota	United States	57201
71	Prairie Lakes Health Care System	Watertown	South Dakota	United States	57201
72	University of Tennessee Medical Center - Cancer Institute	Knoxville	Tennessee	United States	37885
73	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-5505
74	UT Southwestern Medical Center	Dallas	Texas	United States	75390
75	Brooke Army Medical Center Francis Street Medical Center	Fort Sam Houston	Texas	United States	78235-8200
76	Local Institution - 103	Fort Sam Houston	Texas	United States	78235-8200
77	Local Institution - 130	Houston	Texas	United States	77090
78	Northwest Cancer Center	Houston	Texas	United States	77090
79	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
80	Utah Cancer Specialist	Salt Lake City	Utah	United States	84106
81	Huntsman Cancer Institute at the University of Utah	Salt Lake City	Utah	United States	84112
82	Swedish Cancer Inst	Seattle	Washington	United States	98104
83	Medical Oncology Associates	Spokane	Washington	United States	99208
84	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
85	Local Institution - 139	Morgantown	West Virginia	United States	25606
86	West Virginia University CTRU	Morgantown	West Virginia	United States	25606
87	University of Wisconsin	Madison	Wisconsin	United States	53792
88	Local Institution - 136	Milwaukee	Wisconsin	United States	53226
89	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
90	Hospital St. Polten	St. Pölten		Austria	3100
91	Local Institution - 523	St. Pölten		Austria	3100
92	Local Institution - 480	Vienna		Austria	1090
93	Medical University of Vienna	Vienna		Austria	1090
94	Local Institution - 481	Vienna		Austria	1160
95	Wilhelminenspital-Center for Hematology and Oncology	Vienna		Austria	1160
96	RSM Durham Regional Cancer Center - Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
97	CSSS Champlain Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
98	Local Institution - 301	Greenfield Park	Quebec	Canada	J4V 2H1
99	Centre De Sante Et De Services Sociaux De Rimouski-Neigette	Rimouski	Quebec	Canada	G5L5T1
100	Centre Hospitalier Universitaire de Sherbrooke-Hospital Fleurimont	Sherbrooke	Quebec	Canada	J1H5N4
101	Local Institution - 307	Sherbrooke	Quebec	Canada	J1H5N4
102	Local Institution - 304	Halifax		Canada	B3H 2Y9
103	Queen Elizabeth II Health Sciences Centre	Halifax		Canada	B3H 2Y9
104	Aarhus University Hospital	Aarhus		Denmark	8000
105	Copenhagen University Hospital Rigshosptalet	Copenhagen		Denmark	2100
106	Odense University Hospital	Odense		Denmark	DK-5000
107	Local Institution - 499	Vejle		Denmark	7100
108	Vejle Hospital	Vejle		Denmark	7100
109	Helsinki University Central Hospital	Helsinki		Finland	290
110	Local Institution - 455	Helsinki		Finland	290
111	Hyvinkaa Hospital	Hyvinkaa		Finland	05850
112	Centre Hospitalier de la cote basque	Bayonne		France	64109
113	Centre Hospitalier William Morey	Chalon sur Saone		France	71100
114	CHU Hotel	Grenoble Cedex 09		France	38043
115	GH Institut Catholique St Vincent	Lille		France	59000
116	CHRU de Lille-Hopital Claude Huriez	Lille		France	59037
117	Local Institution - 476	Lille		France	59037
118	CHRU Hotel Dieu	Nantes		France	44035
119	Local Institution - 486	Nantes		France	44035
120	Groupement Hospitalier Universitaire Est - Hopital Saint-Antoine	Paris		France	75012
121	Centre Hospitalier Lyon Sud	Pierre-Bénite Cedex		France	69495
122	CHU La Miletrie	Poitiers Cedex		France	86021
123	CHRU Rennes	Rennes		France	35033
124	Local Institution - 504	Rennes		France	35033
125	Institut Universitaire du Cancer de Toulouse (IUCT) - Oncopole	Toulouse Cedex		France	31052
126	CHRU Hopital Bretonneau	Tours cedex		France	37044
127	Local Institution - 468	Tours cedex		France	37044
128	ChariteUniversitatsmedizinCampus Benjamin Franklin	Berlin		Germany	D-13353
129	Local Institution - 442	Berlin		Germany	D-13353
130	Local Institution - 417	Dresden		Germany	01307
131	Universitaetsklinikum Carl Gustav Carus	Dresden		Germany	01307
132	Local Institution - 475	Essen		Germany	45147
133	Universitaetsklinikum EssenInnere Klinik und Poliklinik	Essen		Germany	45147
134	Local Institution - 496	Freiburg		Germany	79106
135	Universitatsklinikum Freiburg	Freiburg		Germany	79106
136	University of Heidelberg	Heidelberg		Germany	69120
137	Local Institution - 410	Tuebingen		Germany	72076
138	UKT Universitaetsklinikum Tuebingen	Tuebingen		Germany	72076
139	General Hospital of Athens Evangelismos	Athens		Greece	10676
140	University of Athens Medical school - Regional General Hospital	Athens		Greece	11528
141	Local Institution - 487	Mezourlo		Greece	41110
142	University General Hospital of Larissa	Mezourlo		Greece	41110
143	George Papanikolaou General Hospital of Thessaloniki	Thessloniki		Greece	57010
144	Local Institution - 465	Thessloniki		Greece	57010
145	Local Institution - 462	Dublin		Ireland	Dublin 7
146	Mater Misericordiae University Hospital	Dublin		Ireland	Dublin 7
147	Local Institution - 431	Dublin		Ireland	Dublin 8
148	St James Hospital	Dublin		Ireland	Dublin 8
149	Local Institution - 413	Galway		Ireland	ST46QG
150	University College Hospital Galway	Galway		Ireland	ST46QG
151	Rambam Health Care Campus	Haifa		Israel	31096
152	Hadassah Medical Center	Jerusalem		Israel	91120
153	Meir Medical Center	Kfar-Saba		Israel	44281
154	Chaim Sheba Medical Center	Ramat Gan		Israel	52621
155	Tel Aviv Sourasky Medical Center Department of Hematology	Tel Aviv		Israel	64239
156	Local Institution - 449	Bergamo		Italy	24127
157	USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII	Bergamo		Italy	24127
158	Local Institution - 456	Bologna		Italy	40138
159	Policlinico S. Orsola - Malpighi	Bologna		Italy	40138
160	Ospedale Ferrarotto	Catania		Italy	95124
161	University of Modena	Modena		Italy	41100
162	IRCCS Policlinico San Matteo	Pavia		Italy	27100
163	Local Institution - 451	Pavia		Italy	27100
164	Azienda Unita Sanitaria Locale (Ausl) Pescara - Presidio Ospedaliero Di Pescara	Pescara		Italy	65124
165	Local Institution - 441	Pescara		Italy	65124
166	Azienda Ospedaliera di Reggio Emilia - Arcispedale Santa Maria Nuova	Reggio Emilia		Italy	42100
167	Local Institution - 414	Reggio Emilia		Italy	42100
168	La Sapienza, University of Rome	Rome		Italy	00161
169	Local Institution - 460	Rome		Italy	00161
170	A.O.U.S. Giovanni e Ruggi d'Aragona UOC UTIC	Salerno		Italy	84131
171	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo		Italy	71013
172	Azienda Ospedaliera S Maria di Terni	Terni		Italy	05100
173	Local Institution - 402	Terni		Italy	05100
174	Azienda Ospedaliera San Giovanni Battista	Torino		Italy	10126
175	Hitachi General Hospital	Hitachi, Ibaraki		Japan	317-0077
176	Kameda Medical Center	Kamogawa		Japan	296-8602
177	Local Institution - 625	Kamogawa		Japan	296-8602
178	Local Institution - 626	Okayama		Japan	701-1192
179	Okayama Medical Center	Okayama		Japan	701-1192
180	Japan Red Cross Medical Center	Shibuya-ku		Japan	150-8935
181	Local Institution - 623	Shibuya-ku		Japan	150-8935
182	National Hospital Organization Disaster Medical Center	Tachikawa		Japan	190-0014
183	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
184	Medisch Centrum Leeuwarden	Leeuwarden		Netherlands	8934 AD
185	Erasmus Medical Center	Rotterdam		Netherlands	3015 CN
186	Local Institution - 494	Rotterdam		Netherlands	3015 CN
187	Oslo universitetssykehus, Rikshospitalet	Oslo		Norway	0372
188	St Olavs Hospital	Trondheim		Norway	7006
189	Szpital Specjalistyczny w Brzozowie	Brzozow		Poland	36-200
190	Szpital Uniwersytecki nr 2 im dr. Jana Biziela	Bydgoszcz		Poland	85-168
191	Zespol Szpitali Miejskich	Chorzow		Poland	41-500
192	Klinika Hematologii Akademii Medycznej w Gdansku	Gdansk		Poland	80-952
193	Oddzial Kliniczny Kliniki Hematologii	Krakow		Poland	31-501
194	Kopernik Memorial Hospital	Lodz		Poland	93-510
195	Klinika Hematoonkologii i Transplantacji Szpiku	Lublin		Poland	20-081
196	Local Institution - 439	Lublin		Poland	20-081
197	Local Institution - 437	Poznan		Poland	60-569
198	Oddzial Hematologii i Chorob Rozrostowych Ukladu Krwiotworczego	Poznan		Poland	60-569
199	Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie	Warszawa		Poland	02-781
200	Hospital de Braga	Braga		Portugal	4710-243
201	Instituto Portugues de Oncologia de Lisboa, Francisco Gentil	Lisboa		Portugal	1099-023
202	Hospital de Santa Maria	Lisboa		Portugal	1649-035
203	Fundacao Champalimaud	Lisbon		Portugal	1400-038
204	Local Institution - 473	Lisbon		Portugal	1400-038
205	Instituto Portugues de Oncologia do Porto, Francisco Gentil	Porto		Portugal	4200-072
206	Hospital de Santo Antonio- Porto	Porto		Portugal
207	Ad-Vance Medical Research, LLC	Ponce		Puerto Rico	00717
208	City Clinical Hospital 52	Moscow		Russian Federation	123182
209	Local Institution - 517	Moscow		Russian Federation	125284
210	Moscow State Healthcare Institution City clinical hospital n.a. S.P.Botkin	Moscow		Russian Federation	125284
211	State Budgetary Healthcare Institution of Nizhniy Novgorod Region	Nizhny Novgorod		Russian Federation	603126
212	Russian Research Institute of Hematology and Transfusiology of the Federal Biomedical Agency	Saint Petersburg		Russian Federation	191024
213	Hospital Universitari Germans Trias i Pujol Can Ruti	Badalona (Barcelona)		Spain	08916
214	Local Institution - 423	Badalona (Barcelona)		Spain	08916
215	Hospital Clinic de Barcelona	Barcelona		Spain	08036
216	Local Institution - 424	Barcelona		Spain	08036
217	Hospital de Basurto-Osakidetza	Bilbao		Spain	48013
218	Hospital 12 de Octubre	Madrid		Spain	28041
219	Hospital Morales Meseguer	Murcia		Spain	30008
220	Local Institution - 502	Murcia		Spain	30008
221	Complejo Hospitalario De Orense	Orense		Spain	32005
222	Clinica Universidad de Navarra	Pamplona		Spain	31008
223	Complejo Hospitalario Nuestra Senora de Valme	Sevilla		Spain	41014
224	Hospital Universitario y Politecnico La Fe	Valencia		Spain	46026
225	Falu lasarett	Falun		Sweden	79182
226	Sahlgrenska University Hospital	Gothenburg		Sweden	60 Gothenburg
227	Local Institution - 429	Luleå		Sweden	SE-971 80
228	Sunderby Sjukhus	Luleå		Sweden	SE-971 80
229	Karolinska University	Stockholm		Sweden	14186
230	Local Institution - 471	Stockholm		Sweden	14186
231	Sundsvalls sjukhus- Medicinkliniken	Sundsvall		Sweden	S-85643
232	Ankara University Medical Faculty Cebeci Hospital	Ankara		Turkey	06590
233	Gazi Universitesi Tip Fakultesi Hastanesi	Ankara		Turkey	6500
234	Local Institution - 409	Ankara		Turkey	6500
235	Ankara Universitesi Tip Fakultesi	Ankara		Turkey	Dikimevi Cebeci
236	Local Institution - 408	Ankara		Turkey	Dikimevi Cebeci
237	Medstar Antalya Hospital	Antalya		Turkey	07050
238	Eskisehir Osmangazi University	Eskisehir		Turkey	26480
239	Local Institution - 421	Gaziantep		Turkey	0
240	Gaziantep University	Gaziantep		Turkey
241	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul		Turkey	34098
242	Istanbul University Faculty of Medicine	Istanbul		Turkey	34390
243	Local Institution - 474	Istanbul		Turkey	34390
244	Ege University Medical School	Izmir		Turkey	35100
245	Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi	Trabzon		Turkey	61080
246	The Royal Bournemouth Hospital	Bournemouth		United Kingdom	BH7 7DW
247	Kent and Canterbury Hospital	Canterbury Kent		United Kingdom	CT1 3NG
248	Local Institution - 479	Canterbury Kent		United Kingdom	CT1 3NG
249	Local Institution - 406	Edinburgh Scotland		United Kingdom	EH4 2XU
250	Western General Hospital	Edinburgh Scotland		United Kingdom	EH4 2XU
251	Local Institution - 490	London		United Kingdom	NW1 2PG
252	University College London Hospitals	London		United Kingdom	NW1 2PG
253	Kings College Hospital	London		United Kingdom	SE5 9RS
254	Local Institution - 512	Oxford		United Kingdom	OX3 7DQ
255	University of Oxford	Oxford		United Kingdom	OX3 7DQ
256	Derriford Hospital Plymouth Oncology Centre Clinical Trials Unit	Plymouth		United Kingdom	PL6 8DH
257	Local Institution - 515	Plymouth		United Kingdom	PL6 8DH
258	Local Institution - 500	Sheffield		United Kingdom	S10 2JF
259	Sheffield Teaching Hospitals NHS Foundation Trust - Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF
260	Local Institution - 493	Southampton		United Kingdom	SO16 6YD
261	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
262	University Hospital of North Staffordshire Nhs Trust - City General Hospital	Stoke-On-Trent		United Kingdom	ST4 6QG
263	Singleton Hospital	Swansea		United Kingdom	SA2 8QA
264	Local Institution - 482	Wolverhampton		United Kingdom	WV10 OPQ
265	New Cross Hospital	Wolverhampton		United Kingdom	WV10 OPQ
266	Worcestershire Acute Hospitals NHS Trust	Worcester		United Kingdom	WR5 1DD