CHRONOS-4: Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess whether copanlisib in combination with standard immunochemotherapy (rituximab in combination with bendamustine [R-B] and rituximab in combination with a 4 drug combination of cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone [R-CHOP]) is effective and safe, compared with placebo in combination with standard immunochemotherapy (R-B or R-CHOP) in patients with relapsed iNHL who have received at least one, but at most three, lines of treatment, including rituximab-based immunochemotherapy and alkylating agents.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Patients should be in need of and fit for immunochemotherapy and should not be resistant to rituximab (resistance defined as lack of response or progression within 6 months of the last date of rituximab administration, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody).
This study will be composed of two parts: Safety run-in and phase III part. The purpose of the safety run-in part of this study is to assess whether the drug being tested (copanlisib) in combination with standard immunochemotherapy (R-B or R-CHOP) is safe and at what dose level of the study drug (copanlisib - 45mg or 60 mg) patients are able to tolerate the study treatment combination. In addition to finding a safe and tolerable dose level for the phase III part of the study, efficacy will also be evaluated for patients that stay on the study treatment during the safety run-in. The phase III part of the study started with the determined recommended dose of copanlisib of 60 mg in combination with R-B. Combination treatment of copanlisib at the recommended/approved dose of 60 mg with R-B or R-CHOP was completed in April 2021.
A maximum of 24 patients will take part in the safety run-in part of this study. In the phase III part approximately 520 patients will be randomly assigned to blinded treatment arms of copanlisib plus R-B or R-CHOP or placebo plus R-B or R-CHOP. Combination therapy (copanlisib/placebo with R-B or R-CHOP) will be administered for a maximum of 6 cycles (C1-C6). Copanlisib/placebo (study drug) monotherapy will be administered from C7 onwards.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Copanlisib + R-B or R-CHOP / Arm 1 Combination of copanlisib with standard immunochemotherapy (rituximab and bendamustine) [R-B] or rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP] (safety run-in and phase III) |
Drug: Copanlisib (BAY80-6946)
Copanlisib is supplied as lyophilized preparation in a 6 mL injection vial. The total amount of copanlisib per vial is 60 mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. For patients on R-B dosing of copanlisib will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered and then rituximab followed by bendamustine. For patients on R-CHOP dosing of copanlisib will be administered on Days 1 and 8 of each 21-day cycle. Treatment with copanlisib/placebo will be continued up to 12 months.
Copanlisib will be administered before rituximab followed by cyclophosphamide, doxorubicin and vincristine infusions. Prednisone/prednisolone tablets to be taken for 5 days.
Drug: Rituximab
Rituximab is administered as an infusion at a dose of 375 mg/m2 body surface on Day 1 of each 28-day cycle for patients assigned to R-B and on Day 2 of each 21-day cycle for patients assigned to R-CHOP.
Drug: Cyclophosphamide
Cyclophosphamide is administered as an infusion at a dose of 750 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Drug: Doxorubicin
Doxorubicin is administered as an infusion at a dose of 50 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Drug: Vincristine
Vincristine is administered as an infusion at a dose of 1.4 mg/m2 body surface (maximum dose 2.0 mg) on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Drug: Bendamustine
Bendamustine is administered as an infusion at a dose of 90 mg/m2 body surface on Day 1 and Day 2 for patients assigned to R-B
Drug: Prednisone
Prednisone is given as 100 mg tablets daily from Day 2 to Day 6 for patients assigned to R-CHOP
|
| Placebo Comparator: Placebo + R-B or R-CHOP / Arm 2 Combination of placebo and R-B or R-CHOP (phase III only) |
Drug: Placebo
Placebo is supplied as lyophilized preparation in a 6 mL injection vial. The developed placebo lyophilisate is equivalent to the 60 mg copanlisib formulation, with regard to the composition of excipients and the instructions for reconstitution and dose preparation. Placebo dosing will be administered as per copanlisib described above. Applies to the phase III part of the study only.
Drug: Rituximab
Rituximab is administered as an infusion at a dose of 375 mg/m2 body surface on Day 1 of each 28-day cycle for patients assigned to R-B and on Day 2 of each 21-day cycle for patients assigned to R-CHOP.
Drug: Cyclophosphamide
Cyclophosphamide is administered as an infusion at a dose of 750 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Drug: Doxorubicin
Doxorubicin is administered as an infusion at a dose of 50 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Drug: Vincristine
Vincristine is administered as an infusion at a dose of 1.4 mg/m2 body surface (maximum dose 2.0 mg) on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Drug: Bendamustine
Bendamustine is administered as an infusion at a dose of 90 mg/m2 body surface on Day 1 and Day 2 for patients assigned to R-B
Drug: Prednisone
Prednisone is given as 100 mg tablets daily from Day 2 to Day 6 for patients assigned to R-CHOP
|
Outcome Measures
Primary Outcome Measures
- Safety run-in_Determination of the recommended Phase-III dose (RP3D) of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicities / adverse events [At Cycle 1: 21 days or 28 days]
- Phase III_Evaluation whether copanlisib in combination with standard immunochemotherapy is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS) [Up to 52 months]
Progression free survival is defined as the time (in days) from randomization to disease progression or death from any cause (if no progression documented).
Secondary Outcome Measures
- Safety run-in_Best Overall Response (BOR) [After Cycle 1: Up to 12 months]
- Safety run-in_Number of participants with treatment-emergent adverse events [Up to 13 months]
- Phase III_Objective tumor response rate (ORR) [Up to 52 months]
Proportion of patients who have a best overall response over the whole duration of the study (i.e. up to time of analysis of PFS) of complete response (CR) or partial response (PR) according to the Lugano Classification and for patients with Waldenström macroglobulinemia a best overall response of CR, very good partial response (VGPR), PR, or minor response (MR) according to the Owen Criteria.
- Phase III_Duration of tumor response (DOR) [Up to 52 months]
Time (in days) from first observed tumor response (complete response [CR], very good partial response [VGPR], partial response [PR], or minor response [MR]) until PD or death from any cause, whichever is earlier. DOR will only be analyzed for patients with at least one CR, VGPR, PR, or MR.
- Phase III_Complete tumor response rate (CRR) [Up to 52 months]
Proportion of patients who have a best overall response of CR during the study (i.e., up to time of analysis of PFS).
- Phase III_Time to tumor progression (TTP) [Up to 52 months]
Time from randomization to PD or death related to PD, whichever is earlier.
- Phase III_Time to next anti-lymphoma treatment (TTNT) [Up to 52 months]
Time from stop of study medication to start of new anti-lymphoma therapy.
- Phase III_Overall survival (OS) [Up to 5 years after last patient´s first treatment]
The time (in days) from randomization until death from any cause.
- Phase III_Time to improvement in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire [Up to 52 months]
Time to improvement in disease-related physical symptoms (DRS-P) is defined as time from randomization to first increase in DRS-P score of at least 3 points from baseline before tumor progression. Will be evaluated for patients with a baseline DRS-P score of 30 points or less. The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire measures disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma.
- Phase III_Time to deterioration in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire [Up to 52 months]
Time to deterioration in disease-related physical symptoms (DRS-P) is defined as time (in days) from randomization to the earliest occurrence of 1) first reduction of DRS-P score from baseline ≥ 3 points, or 2) radiological progression or biochemical progression for Waldenström macroglobulinemia patients without lesions evaluable by imaging, or 3) death from any cause. The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire measures disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma.
- Phase III_Number of participants with treatment-emergent adverse events [Up to 52 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed diagnosis of B lymphocyte antigen CD20 positive iNHL with histological subtype limited to:
-
Follicular lymphoma G1-2-3a
-
Small lymphocytic lymphoma with absolute lymphocyte count <5x10E9/L at study entry
-
Lymphoplasmacytoid lymphoma / Waldenström macroglobulinemia (LPL / WM)
-
Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
-
Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody (e.g. obinutuzumab) -based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody can be considered a previous regimen in the case the patient responded to it); at least 2 consecutive cycles of polychemotherapy; autologous transplant; or radioimmunotherapy. Previous exposure to other PI3K Inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor.
-
Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
-
Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal and positive immunofixation test.
-
Male or female patients ≥ 18 years of age
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
-
Life expectancy of at least 3 months
-
Availability of fresh tumor tissue and/or archival tumor tissue at Screening
-
Adequate baseline laboratory values as assessed within 7 days before starting study treatment.
-
Left ventricular ejection fraction ≥ 50%
Exclusion Criteria
-
Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of transformed disease, a fresh biopsy is recommended.
-
Rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody (e.g. obinutuzumab) resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last date of rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody administration, including maintenance with these drugs).
-
HbA1c > 8.5% at screening
-
History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
-
Known lymphomatous involvement of the central nervous system
-
Known history of human immunodeficiency virus (HIV) infection
-
Hepatitis B (HBV) or hepatitis C (HCV) infection. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
-
Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.CMV PCR test is considered positive if, the result can be interpreted as a CMV viremia according to local standard of care.
-
Uncontrolled hypertension despite optimal medical management (per investigator´s assessment)
-
Congestive heart failure > New York Heart Association (NYHA) class 2
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ironwood Physicians P.C. DBA Ironwood Cancer & Res. Ctr. | Chandler | Arizona | United States | 85224 |
| 2 | Brian J. LeBerthon, MD | West Covina | California | United States | 91790 |
| 3 | SCL Health Research at St Joseph's Hospital Denver CO | Denver | Colorado | United States | 80218 |
| 4 | Lewis Hall Singletary Oncology Center | Thomasville | Georgia | United States | 31792 |
| 5 | Memorial Sloan Kettering Cancer Center- Bergen | Montvale | New Jersey | United States | 07645 |
| 6 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 7 | New York Cancer and Blood Specialists | Port Jefferson Station | New York | United States | 11776 |
| 8 | Gabrail Cancer Center | Canton | Ohio | United States | 44718 |
| 9 | Oncology Consultants | Houston | Texas | United States | 77030 |
| 10 | Texas Oncology- McAllen | McAllen | Texas | United States | 78503 |
| 11 | Calvary Mater Hospital Newcastle | Waratah | New South Wales | Australia | 2298 |
| 12 | Flinders Medical Centre | Adelaide | South Australia | Australia | 5042 |
| 13 | Ashford Cancer Centre Research Pty Ltd | Kurralta Park | South Australia | Australia | 5037 |
| 14 | The Alfred Hospital | Prahran | Victoria | Australia | 3181 |
| 15 | Fiona Stanley Hospital | Murdoch | Western Australia | Australia | 6150 |
| 16 | Eastern Health Integrated Renal Service | Box Hill | Australia | 3128 | |
| 17 | Institut Jules Bordet/Jules Bordet Instituut | Bruxelles - Brussel | Belgium | 1000 | |
| 18 | UZ Gent | Gent | Belgium | 9000 | |
| 19 | UZ Leuven Gasthuisberg | Leuven | Belgium | 3000 | |
| 20 | CHU de Liège | Liege | Belgium | 4000 | |
| 21 | Centro Integrado de Oncologia de Curitiba | Curitiba | Parana | Brazil | 80810-050 |
| 22 | Irmandade Santa Casa de Misericordia de Porto Alegre | Porto Alegre | Rio Grande Do Sul | Brazil | 90050 170 |
| 23 | Hospital de Clínicas de Porto Alegre | Porto Alegre | Rio Grande Do Sul | Brazil | |
| 24 | Centro de Pesquisas Oncológicas | Florianópolis | Santa Catarina | Brazil | 88034-000 |
| 25 | Faculdade de Ciencias Medicas-Universidade Estadual Campinas | Campinas | Sao Paulo | Brazil | 130839 970 |
| 26 | Centro Multidisciplinar de Estudos Clínicos EPP - Ltda. | Santo Andre | Sao Paulo | Brazil | |
| 27 | IEP São Lucas | São Paulo | Sao Paulo | Brazil | 01236-030 |
| 28 | Hospital das Clínicas da Faculdade de Medicina da USP | São Paulo | Sao Paulo | Brazil | 05403-000. |
| 29 | Instituto Nacional do Cancer Jose Alencar Gomes da Silva | Rio de Janeiro | Brazil | 20230 130 | |
| 30 | Hospital Israelita Albert Einstein | Sao Paulo | Brazil | 05651-901 | |
| 31 | UMHAT Sveti Georgi | Plovdiv | Bulgaria | 4002 | |
| 32 | University Multiprofile Hosp. for Active Treat. Sveti Ivan | Sofia | Bulgaria | 1431 | |
| 33 | SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD | Sofia | Bulgaria | 1756 | |
| 34 | Multiprofile Hospital for Active Treatment Hristo Botev AD | Vratsa | Bulgaria | 3000 | |
| 35 | Hopital du Sacre-Coeur de Montreal | Montreal | Quebec | Canada | H4J 1C5 |
| 36 | Recherche soins intensifs, hôpital Maisonneuve-Rosemont | Montréal | Quebec | Canada | H1T 2M4 |
| 37 | Hopital de L'Enfant Jesus | Quebec City | Quebec | Canada | G1J 1Z4 |
| 38 | Centre Universitaire de Sante de l'Estrie | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 39 | Sociedad de Investigaciones Medicas Ltda | Temuco | Araucanía | Chile | 4810469 |
| 40 | Centro de Investigaciones Clínicas Vina del Mar Ltda. | Vina del Mar | Valparaíso | Chile | 2540364 |
| 41 | Instituto Nacional del Cáncer | Santiago | Chile | 838-0455 | |
| 42 | FuJian Medical University Union Hospital | Fuzhou | Fujian | China | 350001 |
| 43 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
| 44 | Guangdong Provincial People's Hospital | Guangzhou | Guangdong | China | 510100 |
| 45 | Tumor Hospital of Hebei Province | Shijiazhuang | Hebei | China | 050011 |
| 46 | Henan Cancer Hospital | Zhengzhou | Henan | China | 450008 |
| 47 | Jiangsu Cancer Hospital | Nanjing | Jiangsu | China | 210009 |
| 48 | 1st Affiliated hospital of Soochow University | Suzhou | Jiangsu | China | 215006 |
| 49 | Jilin Cancer Hospital | Changchun | Jilin | China | 130000 |
| 50 | The Affiliated Hospital of Qingdao University | Qingdao | Shandong | China | 266500 |
| 51 | West China Hospital Sichuan University | Chengdu | Sichuan | China | 610041 |
| 52 | The 1st Affiliated Hospital of Zhejiang University | Hangzhou | Zhejiang | China | 310003 |
| 53 | Zhejiang Cancer Hospital | Hangzhou | Zhejiang | China | 310022 |
| 54 | Beijing Friendship Hospital, Capital Medical University | Beijing | China | 100050 | |
| 55 | Fifth Medical Center, General Hospital of the Chinese People | Beijing | China | 100071 | |
| 56 | Fudan University Shanghai Cancer Center | Shanghai | China | 200030 | |
| 57 | Xinhua Hos Affiliated to SH Jiaotong Uni School of Medicine | Shanghai | China | 200092 | |
| 58 | Tianjin Medical University Cancer Institiute & Hospital | Tianjin | China | 300060 | |
| 59 | Tianjin Union Medicine Centre (People's Hospital of Tianjin) | Tianjin | China | 300121 | |
| 60 | Fakultni Nemocnice Hradec Kralove | Hradec Kralove | Czechia | 50005 | |
| 61 | Fakultni nemocnice Kralovske Vinohrady | Praha 10 | Czechia | 100 34 | |
| 62 | Rigshospitalet | Copenhagen | Denmark | 2100 | |
| 63 | Odense OUH, Haematologisk afdeling | Odense C | Denmark | 5000 | |
| 64 | HUS, Meilahden sairaala | Helsinki | Finland | 00290 | |
| 65 | Oulun yliopistollinen sairaala | Oulu | Finland | 90020 | |
| 66 | Tampereen yliopistollinen sairaala, keskussairaala | Tampere | Finland | 33521 | |
| 67 | Turun yliopistollinen keskussairaala, kantasairaala | Turku | Finland | 20520 | |
| 68 | Centre Hospitalier Universitaire - Angers | Angers | France | 49100 | |
| 69 | Centre Hospitalier de la Durance - Avignon | Avignon | France | 84000 | |
| 70 | Centre Hospitalier Intercommunal de la Côte Basque-Bayonne | Bayonne | France | 64100 | |
| 71 | Centre Hospitalier Universite de Grenoble | Grenoble | France | 38043 | |
| 72 | Clinique Victor Hugo - Le Mans | Le Mans Cedex 2 | France | 72015 | |
| 73 | Hôpital Dupuytren | Limoges Cedex | France | 87042 | |
| 74 | Hôpital Saint-Eloi | Montpellier Cedex | France | 34295 | |
| 75 | Hopital Hotel Dieu - Nantes | Nantes Cedex | France | 44093 | |
| 76 | Hôpital Saint Louis | Paris | France | 75010 | |
| 77 | Centre François Magendie - Pessac | Pessac | France | 33600 | |
| 78 | Hôpital de la Milétrie | Poitiers | France | 86021 | |
| 79 | Clinique Saint Anne | Strasbourg | France | 67000 | |
| 80 | Stauferklinikum Schwäbisch-Gmünd | Mutlangen | Baden-Württemberg | Germany | 73557 |
| 81 | Gemeinschaftspraxis Dr.Heinrich/ Prof.Bangerter | Augsburg | Bayern | Germany | 86150 |
| 82 | Klinikum der Universität München Grosshadern | München | Bayern | Germany | 81377 |
| 83 | Medizinische Hochschule Hannover (MHH) | Hannover | Niedersachsen | Germany | 30625 |
| 84 | Marienhospital Herne Universitätsklinik | Herne | Nordrhein-Westfalen | Germany | 44625 |
| 85 | Universitätsklinikum Münster (UKM) | Münster | Nordrhein-Westfalen | Germany | 48149 |
| 86 | Oncologianova GmbH | Recklinghausen | Nordrhein-Westfalen | Germany | 45659 |
| 87 | Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg | Halle | Sachsen-Anhalt | Germany | 06120 |
| 88 | EVANGELISMOS General Hospital of Athens | Athens | Greece | 106 76 | |
| 89 | LAIKO General Hospital of Athens | Athens | Greece | 115 26 | |
| 90 | University General Hospital of Athens "ATTIKON" | Chaidari | Greece | 12462 | |
| 91 | Univ. General Hospital of Larissa | Larissa | Greece | 41100 | |
| 92 | University General Hospital of Patras | Patras | Greece | 26500 | |
| 93 | Prince of Wales Hospital Hong Kong | Shatin | Hong Kong | ||
| 94 | Semmelweis University | Budapest | Hungary | 1083 | |
| 95 | Semmelweis University | Budapest | Hungary | 1088 | |
| 96 | Orszagos Onkologiai Intezet | Budapest | Hungary | 1122 | |
| 97 | Somogy Megyei Kaposi Mor Oktato Korhaz | Kaposvar | Hungary | 7400 | |
| 98 | SzSzBMK es EOK Josa Andras Oktatokorhaz | Nyiregyhaza | Hungary | 4400 | |
| 99 | Pecsi Tudomanyegyetem Klinikai Kozpont | Pecs | Hungary | 7624 | |
| 100 | Szent Borbala Hospital | Tatabanya | Hungary | 2800 | |
| 101 | Cork University Hospital | Cork | Ireland | ||
| 102 | Mater Misericordiae Hospital | Dublin | Ireland | D07 R2WY | |
| 103 | Rambam Health Corporation | Haifa | Israel | 3109601 | |
| 104 | Hadassah Hebrew University Hospital Ein Kerem | Jerusalem | Israel | 9112001 | |
| 105 | Chaim Sheba Medical Center | Ramat Gan | Israel | 5262000 | |
| 106 | Shamir Medical Center (Assaf Harofeh) | Zerifin | Israel | 6093000 | |
| 107 | IRCCS Ospedale Policlinico San Martino | Genova | Liguria | Italy | 16132 |
| 108 | Istituto Clinico Humanitas - Humanitas Mirasole S.p.A. | Milano | Lombardia | Italy | 20089 |
| 109 | Fondazione IRCCS Policlinico San Matteo | Pavia | Lombardia | Italy | 27100 |
| 110 | A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi" | Ancona | Marche | Italy | 60126 |
| 111 | Aichi Cancer Center Hospital | Nagoya | Aichi | Japan | 464-8681 |
| 112 | Nagoya City University Hospital | Nagoya | Aichi | Japan | 467-8602 |
| 113 | JCHO Kyushu Hospital | Kitakyushu | Fukuoka | Japan | 806-8501 |
| 114 | Gunma University Hospital | Maebashi | Gunma | Japan | 371-8511 |
| 115 | Hyogo Cancer Center | Akashi | Hyogo | Japan | 673-8558 |
| 116 | Kobe University Hospital | Kobe | Hyogo | Japan | 650-0017 |
| 117 | Kanagawa Cancer Center | Yokohama | Kanagawa | Japan | 241-8515 |
| 118 | Tohoku University Hospital | Sendai | Miyagi | Japan | 980-8574 |
| 119 | Tenri Hospital | Tenri | Nara | Japan | 632-8552 |
| 120 | Kindai University Hospital | Osakasayama | Osaka | Japan | 589-8511 |
| 121 | Saitama Medical University International Medical Center | Hidaka | Saitama | Japan | 350-1298 |
| 122 | National Cancer Center Hospital | Chuo-ku | Tokyo | Japan | 104-0045 |
| 123 | Aomori Prefectural Central Hospital | Aomori | Japan | 030-8553 | |
| 124 | National Hospital Organization Kyushu Cancer Center | Fukuoka | Japan | 811-1395 | |
| 125 | Hiroshima Red Cross & Atomic-bomb Survivors Hospital | Hiroshima | Japan | 730-8619 | |
| 126 | National Hospital Organization Kumamoto Medical Center | Kumamoto | Japan | 860-0008 | |
| 127 | Kumamoto University Hospital | Kumamoto | Japan | 860-8556 | |
| 128 | Osaka Red Cross Hospital | Osaka | Japan | 543-8555 | |
| 129 | Osaka Metropolitan University Hospital | Osaka | Japan | 545-8586 | |
| 130 | Yamagata University Hospital | Yamagata | Japan | 990-9585 | |
| 131 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | 03722 | |
| 132 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 133 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
| 134 | Seoul National University Hospital | Seoul | Korea, Republic of | 110-744 | |
| 135 | Hospital General de México SS | Ciudad de México | Distrito Federal | Mexico | 06729 |
| 136 | Centro de Investigación Clínica Chapultepec S.A. de C.V. | Morelia | Michoacán | Mexico | 58260 |
| 137 | Hospital Universitario "José Eleuterio González" | Monterrey | Nuevo Leon | Mexico | 64460 |
| 138 | Centro Especializado en Investigación Clínica S.C. | Boca del Río | Veracruz | Mexico | 94290 |
| 139 | Centro de Atencion e Investigacion Clinica en Oncologia SCP | Merida | Yucatán | Mexico | 97134 |
| 140 | Szpital Morski im. PCK | Gdynia | Poland | 81-519 | |
| 141 | Malopolskie Centrum Medyczne | Krakow | Poland | 30-510 | |
| 142 | Wojew. Szpital Specjalistyczny im. M. Kopernika | Lodz | Poland | 93-513 | |
| 143 | Centro Clinico Academico - Braga | Braga | Portugal | 4710-243 | |
| 144 | Centro Hospitalar Universitario do Porto | Porto | Portugal | 4099-001 | |
| 145 | IPO Porto | Porto | Portugal | 4200-072 | |
| 146 | CHVNGE - Hospital Eduardo Santos Silva | Vila Nova de Gaia | Portugal | 4434-502 | |
| 147 | Sp. Judetean de Urgenta Dr. Constantin Opris Baia Mare | Baia Mare | Romania | 430031 | |
| 148 | S.C. Policlinica de Diagnostic Rapid S.A. | Brasov | Romania | 500152 | |
| 149 | Fundeni Clinical Institute | Bucharest | Romania | 022328 | |
| 150 | Spitalul Clinic Coltea | Bucharest | Romania | 030171 | |
| 151 | Spitalul Clinic Colentina | Bucuresti | Romania | 020125 | |
| 152 | Spitalul Clinic Municipal Filantropia Craiova | Craiova | Romania | 200143 | |
| 153 | Institutul Regional de Oncologie Iasi | Iasi | Romania | 700111 | |
| 154 | Spitalul Clinic Judetean de Urgenta Sibiu | Sibiu | Romania | 550245 | |
| 155 | Kemerovo Regional Clinical Hospital | Kemerovo | Russian Federation | 650066 | |
| 156 | Clinical Oncological Dispensary of Omsk Region | Omsk | Russian Federation | 644013 | |
| 157 | Research Institute of Oncology | Rostov-on-Don | Russian Federation | 344037 | |
| 158 | RSRI of Hematology and Transfusiology | Saint-Petersburg | Russian Federation | 191024 | |
| 159 | Oncology Dispensary #2 | Sochi | Russian Federation | 354057 | |
| 160 | Siberian State Medical University | Tomsk | Russian Federation | 634050 | |
| 161 | Republican Clinical Oncology Dispensary Ufa | Ufa | Russian Federation | 450054 | |
| 162 | National University Hospital | Singapore | Singapore | 119228 | |
| 163 | National Cancer Center Singapore | Singapore | Singapore | 169610 | |
| 164 | Singapore General Hospital | Singapore | Singapore | 169856 | |
| 165 | Narodny onkologicky ustav | Bratislava | Slovakia | 833 10 | |
| 166 | Outeniqua Cancercare Oncology Unit | George | Eastern Cape | South Africa | 6530 |
| 167 | Cancercare Langenhoven | Port Elizabeth | Eastern Cape | South Africa | 6045 |
| 168 | Albert Alberts Stem Cell Transplant Research Centre | Pretoria | Gauteng | South Africa | 0044 |
| 169 | Constantiaberg Medi Clinic | Cape Town | Western Cape | South Africa | 7800 |
| 170 | Institut Català d'Oncologia Badalona | Badalona | Barcelona | Spain | 08916 |
| 171 | Institut Català d'Oncologia Hospitalet | L'Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 172 | Hospital Universitario Clinica Puerta de Hierro | Majadahonda | Madrid | Spain | 28222 |
| 173 | Hospital Regional de Malaga | Oncologia | Malaga | Málaga | Spain | 29010 |
| 174 | Ciutat Sanitària i Universitaria de la Vall d'Hebron | Barcelona | Spain | 08035 | |
| 175 | Hospital Clínico Universitario Lozano Blesa | Zaragoza | Spain | 50009 | |
| 176 | Changhua Christian Hospital | Changhua | Taiwan | 50006 | |
| 177 | Chang Gung Memorial Hospital Kaohsiung | Kaohsiung | Taiwan | 833 | |
| 178 | National Cheng Kung University Hospital | Tainan | Taiwan | 704 | |
| 179 | National Taiwan University Hospital | Taipei | Taiwan | 10002 | |
| 180 | Taipei Veterans General Hospital | Taipei | Taiwan | 11217 | |
| 181 | Pramongkutklao Hospital | Bangkok | Thailand | 10400 | |
| 182 | Siriraj Hospital, Mahidol | Bangkok | Thailand | 10700 | |
| 183 | Ankara Universitesi Tip Fakultesi Hastanesi | Ankara | Turkey | 06100 | |
| 184 | Trakya Univ. Tip Fak. | Edirne | Turkey | 22030 | |
| 185 | Istanbul Universitesi Istanbul Tip Fakultesi | Istanbul | Turkey | 34093 | |
| 186 | Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi | Istanbul | Turkey | 34899 | |
| 187 | Ege Universitesi Tip Fakultesi | Izmir | Turkey | 35100 | |
| 188 | Dokuz Eylul Universitesi Tip Fakultesi | Izmir | Turkey | 35340 | |
| 189 | Erciyes Universitesi Tip Fakultesi | Kayseri | Turkey | 38039 | |
| 190 | Ondokuz Mayis Uni Tip Fakultesi | Samsun | Turkey | 55139 | |
| 191 | Karadeniz Teknik Universitesi Tip Fakultesi | Trabzon | Turkey | 61080 | |
| 192 | Cherkasy Oncological Dispensary | Cherkasy | Ukraine | 18009 | |
| 193 | Multidisciplinary Clinical Hosp. 4 Dnipro | Dnipro | Ukraine | 49102 | |
| 194 | National Cancer Institute-Ukraine | Kiev | Ukraine | 03022 | |
| 195 | Institute of Blood Pathology and Transfusion medicine | Lviv | Ukraine | 79044 | |
| 196 | Zaporizhzhia Regional Clinical Hospital | Zaporizhzhya | Ukraine | 69600 | |
| 197 | Royal Devon & Exeter Hospital | Exeter | Devon | United Kingdom | EX2 5AX |
| 198 | Northwick Park Hospital | Harrow | London | United Kingdom | HA1 3UJ |
| 199 | Dorset County Hospital | Dorchester | United Kingdom | DT1 2JY | |
| 200 | St. George's Hospital | London | United Kingdom | SW17 OQT | |
| 201 | Singleton Hospital | Swansea | United Kingdom | SA2 8QA |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 17833
- 2015-001088-38