Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)

Phase 3

Terminated

Conditions: Lymphoma, Non-Hodgkin

Interventions: Drug: Copanlisib (BAY80-6946)
Drug: Placebo
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Bendamustine
Drug: Prednisone

Registration Number: NCT02626455

Lead Sponsor: Bayer

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 551

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Copanlisib + R-B or R-CHOP / Arm 1	Copanlisib (BAY80-6946)	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)
Placebo + R-B or R-CHOP / Arm 2	Placebo	Combination of placebo and R-B or R-CHOP (phase III only)
Placebo + R-B or R-CHOP / Arm 2	Bendamustine	Combination of placebo and R-B or R-CHOP (phase III only)
Copanlisib + R-B or R-CHOP / Arm 1	Rituximab	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)
Copanlisib + R-B or R-CHOP / Arm 1	Cyclophosphamide	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)
Copanlisib + R-B or R-CHOP / Arm 1	Doxorubicin	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)
Copanlisib + R-B or R-CHOP / Arm 1	Vincristine	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)
Placebo + R-B or R-CHOP / Arm 2	Doxorubicin	Combination of placebo and R-B or R-CHOP (phase III only)
Copanlisib + R-B or R-CHOP / Arm 1	Bendamustine	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)
Copanlisib + R-B or R-CHOP / Arm 1	Prednisone	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)
Placebo + R-B or R-CHOP / Arm 2	Rituximab	Combination of placebo and R-B or R-CHOP (phase III only)
Placebo + R-B or R-CHOP / Arm 2	Cyclophosphamide	Combination of placebo and R-B or R-CHOP (phase III only)
Placebo + R-B or R-CHOP / Arm 2	Vincristine	Combination of placebo and R-B or R-CHOP (phase III only)
Placebo + R-B or R-CHOP / Arm 2	Prednisone	Combination of placebo and R-B or R-CHOP (phase III only)

Primary Outcome Measures

Name	Time	Method
SRI: Occurrence of Dose-limiting Toxicities (DLT)	At Cycle 1: 28 days for Copa+R-B or 21 days for Copa+R-CHOP	Dose-limiting toxicity is defined as any of the following occurring during Cycle 1 at a given dose level and regarded by the investigator and/or the sponsor to be possibly, probably, or definitely related to copanlisib given in combination with R-B or R-CHOP. General: any grade 5 hematologic or non-hematologic toxicity or any delay of \>2 weeks of Cycle 2 due to study treatment-related toxicity; Non-hematologic DLT: any non-hematologic toxicity grade ≥ 3; Hematologic DLT: grade 4 absolute neutrophil count decrease lasting \>7 days, or grade 4 febrile neutropenia, or grade 4 platelet count decreased or grade 3 platelet count decreased with serious bleeding, or signs of serious bleeding and/or international normalized ratio (INR) increased or partial thromboplastin time (PTT) prolonged of grade 3.
Phase 3: Progression-free Survival (PFS) by Independent Central Review	Approximately 6 years 4 months	PFS is defined as the time from randomization to progressive disease (PD) or death from any cause (if no progression is documented).

Secondary Outcome Measures

Name	Time	Method
Phase 3: Objective Tumor Response Rate (ORR)-Independent Central Review	Up to 6 years 4 months	ORR, as assessed by independent central review, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS).
SRI: Best Overall Response	Approximately 7 years 8 months	Best overall response is defined as the best response achieved during the treatment and active follow-up periods; prior to end of study or start of new anti-tumor treatment, whichever occurs first.
SRI: Number of Subjects With Treatment-emergent Adverse Event (TEAE)	Approximately 4 years 10 months	A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake.
Phase 3: ORR-Investigator Assessment	Up to 6 years 4 months	ORR, as assessed by investigator, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS).
Phase 3: Duration of Tumor Response (DOR)-Independent Central Review	Approximately 6 years 4 months	DOR, as assessed by independent central review, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR.
Phase 3: DOR-Investigator Assessment	Approximately 6 years 4 months	DOR, as assessed by investigator, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR.
Phase 3: Complete Tumor Response Rate (CRR)-Independent Central Review	Approximately 6 years 4 months	CRR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS).
Phase 3: CRR-Investigator Assessment	Approximately 6 years 4 months	CRR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS).
Phase 3: Disease Control Rate (DCR)-Independent Central Review	Approximately 6 years 4 months	DCR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease).
Phase 3: DCR-Investigator Assessment	Approximately 6 years 4 months	DCR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease).
Phase 3: Time to Tumor Progression (TTP)-Independent Central Review	Approximately 6 years 4 months	TTP, as assessed by independent central review, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of "other" as reason (which excludes PD).
Phase 3: TTP-Investigator Assessment	Approximately 6 years 4 months	TTP, as assessed by investigator, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of "other" as reason (which excludes PD).
Phase 3: Time to Next Anti-lymphoma Treatment (TTNT)	Approximately 6 years 4 months	A new anti-lymphoma therapy is any new systemic anticancer treatment or radiotherapy for lymphoma, with a consolidation intent. TTNT was defined as the time from the date of randomization to the start of new anti-lymphoma therapy, where the date of randomization was considered Day 1.
Phase 3: Overall Survival (OS)	Approximately 6 years 4 months	Overall survival is defined as the time from randomization until death from any cause. The OS for patients alive at the time of the database cut-off date was censored to the last date they were known to be alive. Deaths that occurred after the database cut-off date, reported during data cleaning, were considered for establishing the last known alive date at data cut-off.
Phase 3: Time to Deterioration in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma	Approximately 6 years 4 months	Time to deterioration in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated in all patients. It is defined as the time from randomization to DRS-P decline, progression, or death from any reason, whichever occurred earlier.
Phase 3: Time to Improvement in Disease-related Symptoms-physical (DRS-P) of at Least 3 Points of Lymphoma	Approximately 6 years 4 months	Time to improvement in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated for all patients. It is defined as the time from randomization to DRS-P improvement of at least 3 points.
Phase 3: Number of Subjects With Treatment-emergent Adverse Event (TEAE)	Approximately 4 years	A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake.

Trial Locations

Locations (201): Memorial Sloan Kettering Cancer Center- Bergen
🇺🇸
New York, New York, United States
Hospital de Clinicas de Porto Alegre | Clinical Research Center - Surgery Research Center
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Irmandade da Santa Casa de Misericordia de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Rigshospitalet - Hjertesygdomme
🇩🇰
København Ø, Denmark
Tianjin Medical University Cancer Institute & Hospital
🇨🇳
Tianjin, China
Odense Universitetshospital - Hæmatologisk afdeling
🇩🇰
Odense C, Denmark
Tampereen yliopistollinen sairaala
🇫🇮
Tampere, Finland
Universitaetsklinikum Muenster
🇩🇪
Münster, Nordrhein-Westfalen, Germany
Haematologie-Onkologie im Zentrum MVZ GmbH
🇩🇪
Augsburg, Bayern, Germany
General Hospital of Athens LAIKO
🇬🇷
Athens, Greece
Prince of Wales Hospital
🇭🇰
Hong Kong, Hong Kong
Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz
🇭🇺
Nyiregyhaza, Hungary
Mater Misericordiae University Hospital
🇮🇪
Dublin, Ireland
Humanitas Mirasole S.p.A.
🇮🇹
Milano, Lombardia, Italy
IRCCS Fondazione Policlinico San Matteo
🇮🇹
Pavia, Lombardia, Italy
Pratia McM Kraków
🇵🇱
Krakow, Poland
Centro Clinico Academico Braga | Braga, Portugal
🇵🇹
Braga, Portugal
Republican Clinical Oncology Dispensary
🇷🇺
Ufa, Russian Federation
Centro Hospitalar Vila Nova de Gaia e Espinho | Unit 1 - Clinical Research Center
🇵🇹
Porto, Portugal
Sc Onco Card Srl
🇷🇴
Brasov, Romania
Phramongkutklao Hospital
🇹🇭
Bangkok, Thailand
Marmara Uni. Tip Fak. Pendik EAH Hematoloji BD
🇹🇷
Istanbul, Turkey
Clinic of National cancer institute - scientific and research department of pediatric oncology
🇺🇦
Kyiv, Ukraine
Royal Marsden Hospital (London)
🇬🇧
London, United Kingdom
Municipal Non-Profit Enterprise "City Clinical Hospital ?4" of the Dnipro City Council
🇺🇦
Dnipro, Ukraine
Ironwood Physicians P.C. DBA Ironwood Cancer & Res. Ctr.
🇺🇸
Chandler, Arizona, United States
Brian J. LeBerthon, MD
🇺🇸
West Covina, California, United States
SCL Health Research at St Joseph's Hospital Denver CO
🇺🇸
Denver, Colorado, United States
Lewis Hall Singletary Oncology Center
🇺🇸
Thomasville, Georgia, United States
New York Cancer and Blood Specialists
🇺🇸
Port Jefferson Station, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Gabrail Cancer Center
🇺🇸
Canton, Ohio, United States
Oncology Consultants
🇺🇸
Houston, Texas, United States
Texas Oncology- McAllen
🇺🇸
McAllen, Texas, United States
Calvary Mater Hospital Newcastle
🇦🇺
Waratah, New South Wales, Australia
Flinders Medical Centre
🇦🇺
Bedford Park, South Australia, Australia
Ashford Cancer Centre Research Pty Ltd
🇦🇺
Kurralta Park, South Australia, Australia
The Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Fiona Stanley Hospital
🇦🇺
Murdoch, Western Australia, Australia
Eastern Health Integrated Renal Service
🇦🇺
Box Hill, Australia
Institut Jules Bordet/Jules Bordet Instituut
🇧🇪
Bruxelles, Belgium
UZ Gent
🇧🇪
Gent, Belgium
UZ Leuven Gasthuisberg
🇧🇪
Leuven, Belgium
CHU de Liège
🇧🇪
Liege, Belgium
Centro Integrado de Oncologia de Curitiba
🇧🇷
Curitiba, Parana, Brazil
Faculdade de Ciencias Medicas-Universidade Estadual Campinas
🇧🇷
Campinas, Sao Paulo, Brazil
Centro Multidisciplinar de Estudos Clínicos EPP - Ltda.
🇧🇷
São Bernardo do Campo, Sao Paulo, Brazil
Centro de Pesquisas Oncológicas
🇧🇷
Florianópolis, Santa Catarina, Brazil
IEP São Lucas
🇧🇷
São Paulo, Sao Paulo, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva
🇧🇷
Rio de Janeiro, Brazil
Hospital das Clínicas da Faculdade de Medicina da USP
🇧🇷
Sao Paulo, Brazil
Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department
🇧🇷
Sao Paulo, Brazil
UMHAT Sveti Georgi
🇧🇬
Plovdiv, Bulgaria
University Multiprofile Hosp. for Active Treat. Sveti Ivan
🇧🇬
Sofia, Bulgaria
SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
🇧🇬
Sofia, Bulgaria
Multiprofile Hospital for Active Treatment Hristo Botev AD
🇧🇬
Vratsa, Bulgaria
Hopital du Sacre-Coeur de Montreal
🇨🇦
Montreal, Quebec, Canada
Hopital Maisonneuve-Rosemont
🇨🇦
Montreal, Quebec, Canada
Hopital de L'Enfant Jesus
🇨🇦
Quebec City, Quebec, Canada
Centre Universitaire de Sante de l'Estrie
🇨🇦
Sherbrooke, Quebec, Canada
Centro de Investigaciones Clínicas Vina del Mar Ltda.
🇨🇱
Vina del Mar, Valparaíso, Chile
Sociedad de Investigaciones Medicas Ltda
🇨🇱
Temuco, Araucanía, Chile
Instituto Nacional del Cáncer
🇨🇱
Santiago, Chile
Tumor Hospital of Hebei Province
🇨🇳
Hebei, Hebei, China
Henan Cancer Hospital
🇨🇳
Zhengzhou, Henan, China
Jiangsu Cancer Hospital
🇨🇳
Nanjing, Jiangsu, China
FuJian Medical University Union Hospital
🇨🇳
Fuzhou, Fujian, China
Guangdong Provincial People's Hospital
🇨🇳
Guangzhou, Guangdong, China
Sun Yat-sen University Cancer Center
🇨🇳
Guangzhou, Guangdong, China
1st Affiliated hospital of Soochow University
🇨🇳
Suzhou, Jiangsu, China
Jilin Cancer Hospital
🇨🇳
Changchun, Jilin, China
The Affiliated Hospital of Qingdao University
🇨🇳
Shandong, Shandong, China
The 1st Affiliated Hospital of Zhejiang University
🇨🇳
Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳
Hangzhou, Zhejiang, China
Fifth Medical Center, General Hospital of the Chinese People
🇨🇳
Beijing, China
West China Hospital Sichuan University
🇨🇳
Chengdu, Sichuan, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳
Beijing, China
Fudan University Shanghai Cancer Center
🇨🇳
Shanghai, China
Xinhua Hos Affiliated to SH Jiaotong Uni School of Medicine
🇨🇳
Shanghai, China
Tianjin Union Medicine Centre (People's Hospital of Tianjin)
🇨🇳
Tianjin, China
Fakultni Nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿
Praha 10, Czechia
HUS, Meilahden sairaala
🇫🇮
Helsinki, Finland
Oulun yliopistollinen sairaala
🇫🇮
Oulu, Finland
Turun yliopistollinen keskussairaala
🇫🇮
Turku, Finland
Centre Hospitalier Universitaire - Angers
🇫🇷
Angers, France
Centre Hospitalier de la Durance - Avignon
🇫🇷
Avignon, France
Centre Hospitalier Intercommunal de la Côte Basque-Bayonne
🇫🇷
Bayonne, France
Centre Hospitalier Universite de Grenoble
🇫🇷
Grenoble, France
Clinique Victor Hugo - Le Mans
🇫🇷
Le Mans Cedex 2, France
Hôpital Dupuytren
🇫🇷
Limoges Cedex, France
Hôpital Saint-Eloi
🇫🇷
Montpellier Cedex, France
Hopital Hotel Dieu - Nantes
🇫🇷
Nantes, France
Hôpital Saint Louis
🇫🇷
Paris, France
Centre François Magendie - Pessac
🇫🇷
Pessac, France
Hôpital de la Milétrie
🇫🇷
Poitiers, France
Clinique Saint Anne
🇫🇷
Strasbourg, France
Stauferklinikum Schwäbisch-Gmünd
🇩🇪
Mutlangen, Baden-Württemberg, Germany
Klinikum der Universität München Grosshadern
🇩🇪
München, Bayern, Germany
Medizinische Hochschule Hannover (MHH)
🇩🇪
Hannover, Niedersachsen, Germany
Oncologianova GmbH
🇩🇪
Recklinghausen, Nordrhein-Westfalen, Germany
Marienhospital Herne Universitätsklinik
🇩🇪
Herne, NRW, Germany
Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg
🇩🇪
Halle, Sachsen-Anhalt, Germany
EVANGELISMOS General Hospital of Athens
🇬🇷
Athens, Greece
University General Hospital of Athens "ATTIKON"
🇬🇷
Chaidari, Greece
Univ. General Hospital of Larissa
🇬🇷
Larissa, Greece
University General Hospital of Patras
🇬🇷
Patras, Greece
Semmelweis University
🇭🇺
Budapest, Hungary
Orszagos Onkologiai Intezet
🇭🇺
Budapest, Hungary
Somogy Varmegyei Kaposi Mor Oktato Korhaz
🇭🇺
Kaposvar, Hungary
Pecsi Tudomanyegyetem Klinikai Kozpont
🇭🇺
Pecs, Hungary
Komarom-Esztergom Varmegyei Szent Borbala Korhaz
🇭🇺
Tatabanya, Hungary
Cork University Hospital
🇮🇪
Cork, Ireland
Rambam Health Corporation
🇮🇱
Haifa, Israel
Hadassah Hebrew University Hospital Ein Kerem
🇮🇱
Jerusalem, Israel
Chaim Sheba Medical Center
🇮🇱
Ramat Gan, Israel
IRCCS Ospedale Policlinico San Martino
🇮🇹
Genova, Liguria, Italy
Shamir Medical Center (Assaf Harofeh)
🇮🇱
Zerifin, Israel
A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
🇮🇹
Ancona, Marche, Italy
Aichi Cancer Center Hospital
🇯🇵
Nagoya, Aichi, Japan
Nagoya City University Hospital
🇯🇵
Nagoya, Aichi, Japan
JCHO Kyushu Hospital
🇯🇵
Kitakyushu, Fukuoka, Japan
Gunma University Hospital
🇯🇵
Maebashi, Gunma, Japan
Hyogo Cancer Center
🇯🇵
Akashi, Hyogo, Japan
Kobe University Hospital
🇯🇵
Kobe, Hyogo, Japan
Kanagawa Cancer Center
🇯🇵
Yokohama, Kanagawa, Japan
Tohoku University Hospital
🇯🇵
Sendai, Miyagi, Japan
Tenri Hospital
🇯🇵
Tenri, Nara, Japan
Kindai University Hospital
🇯🇵
Osakasayama-shi, Osaka, Japan
Saitama Medical University International Medical Center
🇯🇵
Hidaka, Saitama, Japan
National Cancer Center Hospital
🇯🇵
Chuo-ku, Tokyo, Japan
Aomori Prefectural Central Hospital
🇯🇵
Aomori, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵
Fukuoka, Japan
Hiroshima Red Cross & Atomic-bomb Survivors Hospital
🇯🇵
Hiroshima, Japan
National Hospital Organization Kumamoto Medical Center
🇯🇵
Kumamoto, Japan
Kumamoto University Hospital
🇯🇵
Kumamoto, Japan
Osaka Red Cross Hospital
🇯🇵
Osaka, Japan
Osaka Metropolitan University Hospital
🇯🇵
Osaka, Japan
Yamagata University Hospital
🇯🇵
Yamagata, Japan
Seoul National University Hospital
🇰🇷
Seoul, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital General de México SS
🇲🇽
México, D. F., Distrito Federal, Mexico
Centro de Investigación Clínica Chapultepec S.A. de C.V.
🇲🇽
Morelia, Michoacán, Mexico
Centro Especializado en Investigación Clínica S.C.
🇲🇽
Boca del Río, Veracruz, Mexico
Hospital Universitario "José Eleuterio González"
🇲🇽
Monterrey, Nuevo Leon, Mexico
Centro de Atencion e Investigacion Clinica en Oncologia SCP
🇲🇽
Merida, Yucatán, Mexico
Szpital Morski im. PCK
🇵🇱
Gdynia, Poland
Wojew. Szpital Specjalistyczny im. M. Kopernika
🇵🇱
Lodz, Poland
Centro Hospitalar Universitario do Porto
🇵🇹
Porto, Portugal
IPO Porto
🇵🇹
Porto, Portugal
Spitalul Clinic Colentina
🇷🇴
Bucuresti, Romania
Sp. Judetean de Urgenta Dr. Constantin Opris Baia Mare
🇷🇴
Baia Mare, Romania
Spitalul Clinic Coltea
🇷🇴
Bucuresti, Romania
Fundeni Clinical Institute
🇷🇴
Bucuresti, Romania
Spitalul Clinic Municipal Filantropia Craiova
🇷🇴
Craiova, Romania
Institutul Regional de Oncologie Iasi
🇷🇴
Iasi, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
🇷🇴
Sibiu, Romania
Kemerovo Regional Clinical Hospital
🇷🇺
Kemerovo, Russian Federation
Research Institute of Oncology
🇷🇺
Rostov-on-Don, Russian Federation
Clinical Oncological Dispensary of Omsk Region
🇷🇺
Omsk, Russian Federation
RSRI of Hematology and Transfusiology
🇷🇺
Saint-Petersburg, Russian Federation
Oncology Dispensary #2
🇷🇺
Sochi, Russian Federation
Siberian State Medical University
🇷🇺
Tomsk, Russian Federation
National University Hospital
🇸🇬
Singapore, Singapore
National Cancer Center Singapore
🇸🇬
Singapore, Singapore
Singapore General Hospital
🇸🇬
Singapore, Singapore
Narodny onkologicky ustav
🇸🇰
Bratislava, Slovakia
Cancercare Langenhoven
🇿🇦
Port Elizabeth, Eastern Cape, South Africa
Albert Alberts Stem Cell Transplant Research Centre
🇿🇦
Pretoria, Gauteng, South Africa
Outeniqua Cancercare Oncology Unit
🇿🇦
George, Eastern Cape, South Africa
Constantiaberg Medi Clinic
🇿🇦
Cape Town, Western Cape, South Africa
Institut Català d'Oncologia Hospitalet
🇪🇸
Hospitalet de Llobregat, Barcelona, Spain
Institut Català d'Oncologia Badalona
🇪🇸
Badalona, Barcelona, Spain
Hospital Universitario Clinica Puerta de Hierro
🇪🇸
Majadahonda, Madrid, Spain
Hospital Regional de Malaga | Oncologia
🇪🇸
Malaga, Málaga, Spain
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Clínico Universitario Lozano Blesa
🇪🇸
Zaragoza, Spain
Changhua Christian Hospital
🇨🇳
Changhua, Taiwan
Chang Gung Memorial Hospital Kaohsiung
🇨🇳
Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Siriraj Hospital, Mahidol
🇹🇭
Bangkok, Thailand
Ankara Universitesi Tip Fakultesi Hastanesi
🇹🇷
Ankara, Turkey
Trakya Univ. Tip Fak.
🇹🇷
Edirne, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi
🇹🇷
Istanbul, Turkey
Dokuz Eylul Universitesi Tip Fakultesi
🇹🇷
Izmir, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷
Izmir, Turkey
Erciyes Universitesi Tip Fakultesi
🇹🇷
Kayseri, Turkey
Ondokuz Mayis Uni Tip Fakultesi
🇹🇷
Samsun, Turkey
Karadeniz Teknik Universitesi Tip Fakultesi
🇹🇷
Trabzon, Turkey
CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"
🇺🇦
Cherkasy, Ukraine
State Institution - Institute of Blood Pathology and Transfusion Medicine NAMS of Ukraine
🇺🇦
Lviv, Ukraine
CNE "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia regional council
🇺🇦
Zaporizhzhya, Ukraine
Royal Devon & Exeter Hospital
🇬🇧
Exeter, Devon, United Kingdom
Northwick Park Hospital
🇬🇧
Harrow, London, United Kingdom
St George's Hospital
🇬🇧
Kogarah, London, United Kingdom
Dorset County Hospital
🇬🇧
Dorchester, United Kingdom
Singleton Hospital
🇬🇧
Swansea, United Kingdom