A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)
- Conditions
- Diffuse Large B-Cell Lymphoma
- Interventions
- Registration Number
- NCT01287741
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This open-label, randomized, parallel group study will evaluate the efficacy and safety of obinutuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone or prednisone (CHOP) chemotherapy versus rituximab (MabThera/Rituxan) with CHOP in previously untreated participants with cluster of differentiation 20 (CD20)-positive diffuse large B-cell lymphoma (DLBCL). Participants will be randomized to receive either obinutuzumab 1000 milligrams (mg) intravenously (IV) every 21 days or rituximab 375 milligrams per square meter (mg/m\^2) IV every 21 days for 8 cycles, in addition to 6-8 cycles of CHOP chemotherapy IV every 21 days. Participants randomized to the obinutuzumab arm will receive an additional two doses on Days 8 and 15 of Cycle 1. Anticipated time on study treatment is 24 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1418
- Previously untreated CD20-positive DLBCL
- At least 1 bi-dimensionally measurable lesion (greater than [>]1.5 centimeters [cm] in its largest dimension on the computed tomography [CT] scan)
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Adequate hematological function
- Low-intermediate, high-intermediate or high-risk International Prognostic Index (IPI) score (low-risk IPI score: IPI 1 irrespective of bulky disease or IPI 0 with bulky disease, defined as one lesion greater than equal to (>/=) 7.5 cm)
- Left ventricular ejection fraction (LVEF) >/=50 percent (%) on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products or to any component of CHOP or obinutuzumab
- Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
- Participants with transformed lymphoma and participants with follicular lymphoma IIIB
- Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
- Prior treatment with cytotoxic drugs or rituximab for another condition (for example, rheumatoid arthritis) or prior use of an anti-CD20 antibody
- Prior use of any monoclonal antibody within 3 months of the start of Cycle 1
- Corticosteroid use of >30 milligrams per day (mg/day) of prednisone or equivalent, for purposes other than lymphoma symptom control
- Primary central nervous system (CNS) lymphoma and secondary CNS involvement by lymphoma, mantle-cell lymphoma (MCL), or histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, plasmablastic lymphoma, and primary cutaneous DLBCL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rituximab+Chemotherapy Rituximab Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Rituximab+Chemotherapy Cyclophosphamide Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Rituximab+Chemotherapy Vincristine Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Rituximab+Chemotherapy Prednisone Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Obinutuzumab+Chemotherapy Cyclophosphamide Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Rituximab+Chemotherapy Doxorubicin Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Obinutuzumab+Chemotherapy Obinutuzumab Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Obinutuzumab+Chemotherapy Doxorubicin Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Obinutuzumab+Chemotherapy Vincristine Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy. Obinutuzumab+Chemotherapy Prednisone Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
- Primary Outcome Measures
Name Time Method Median Time to Progression-Free Survival (PFS), Investigator-Assessed Baseline up to approximately 6.5 years (up to 31 January 2018) Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease \[PD\]). Progression-free survival was defined as the time from randomization until the first documented day of disease progression or relapse, using a modified version of the Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least 50% increase in nodal lesions or \>/=50% increase in any node \> 1 centimeter (cm) or \>/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion \> 1.5 cm or \>/= 50% increase in any previously involved node with a diameter \</= 1 cm such that it is now \>1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).
- Secondary Outcome Measures
Name Time Method Median Time to Overall Survival (OS) Baseline up to approximately 6.5 years (up to 31 January 2018) Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death. Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause.
Median Time to Event-Free Survival (EFS), Investigator-Assessed Baseline up to death or disease progression, or initiation of new anti-lymphoma treatment (NALT), whichever occurred first, approximately 6.5 years (up to 31 January 2018) Kaplan Meier estimate of median EFS is the time at which half of the participants have progressed. Event-free survival was defined as the time from the date of randomization until the date of disease progression, relapse, initiation of a new non-protocol-specified anti-lymphoma treatment, or death from any cause on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or \>/=50% increase in any node \> 1 centimeter (cm) or \>/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion \> 1.5 cm or \>/= 50% increase in any previously involved node with a diameter \</= 1 cm such that it is now \>1.5 cm. Tumor measurements were obtained by CT/MRI.
Median Time to Disease-Free Survival (DFS), Investigator-Assessed Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018) Kaplan Meier estimate of median DFS was defined as time at which half of participants have disease progression/relapse or death from any cause. Disease-free survival was defined as time from date of the first occurrence of a documented CR to date of disease progression/relapse or death from any cause on basis of investigator assessments with use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or \>/=50% increase in any node \> 1 centimeter (cm) or \>/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion \> 1.5 cm or \>/= 50% increase in any previously involved node with a diameter \</= 1 cm such that it is now \>1.5 cm.
Time to Next Anti-Lymphoma Treatment (TTNALT) Baseline up to start of next anti-lymphoma treatment or death due to any cause, whichever occurred first, approximately 6.5 years (31 January 2018) Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause.
Overall Response Rate (ORR), IRC-Assessed Baseline up to approximately 4 years and 9 months (up to 29 April 2016) Overall response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites. This outcome measure used data from primary analysis which included all 1418 participants.
Duration of Response (DOR), Investigator-Assessed Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018) DOR: time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with CT/MRI. CR: disappearance of all target lesions. PR: \>/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodule regression \>/= 50%. Progression/relapse: at least 50% increase in nodal lesions or \>/=50% increase in any node \> 1 cm or \>/= 50% increase in other target lesions (e.g., splenic or hepatic nodules) and/or any new bone marrow involvement and/or any new lesion \> 1.5 cm or \>/= 50% increase in any previously involved node with a diameter \</= 1 cm such that it is now \>1.5 cm. A participant in the Rituximab+CHOP arm with the longest follow-up, 53 months, had an event. The criterion for median was the minimum time when survival went below 50%.
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab Pre-dose (Hour 0) on Cycle (C) 4 Day (D) 1, at end of treatment/early termination (up to Month 6), every 6 months thereafter for 30 months (cycle length = 21 days) The presence of HAHAs to obinutuzumab was assessed in the first 100 randomized participants.
Median Time to Progression-Free Survival (PFS), Independent Review Committee (IRC)-Assessed Baseline up to approximately 4 years and 9 months (up to 29 April 2016) Kaplan Meier estimate of median PFS was defined as time at which half of participants have progressed (progressive disease \[PD\]). Progression-free survival was defined as time from randomization until first documented day of disease progression or relapse, using a modified version of Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on basis of IRC assessments. Progression was defined as at least 50% increase in nodal lesions or \>/=50% increase in any node \> 1 cm or \>/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion \> 1.5 cm or \>/= 50% increase in any previously involved node with diameter \</= 1 cm such that it is now \>1.5 cm. Tumor measurements were obtained by CT or MRI. This outcome measure used data from primary analysis which included all 1418 participants.
Overall Response Rate (ORR), Investigator-Assessed Baseline up to approximately 6.5 years (up to 31 January 2018) Overall response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.
Complete Response (CR) at the End of Treatment, Investigator-Assessed Baseline up to approximately 6.5 years (up to 31 January 2018) Percentage of participants with complete response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease.
Complete Response (CR) at the End of Treatment, IRC-Assessed Baseline up to approximately 4 years and 9 months (up to 29 April 2016) Percentage of participants with complete response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease. This outcome measure used data from primary analysis which included all 1418 participants.
Percentage of Participants With Adverse Events (AEs) Baseline up to approximately 6.5 years (up to 31 January 2018) An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale Score Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to approximately 6.5 years, (cycle length = 21 days) The FACT-Lym subscale was developed to assess health-related quality of life in participants with non-Hodgkin lymphoma. The score range is 0-60, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to data cut-off, up to approximately 6.5 years, (cycle length = 21 days) The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
Serum Concentrations of Obinutuzumab in Japanese Participants With Diffuse Large B-Cell Lymphoma (DLBCL) C1: D1 post-infusion and 20-28 and 66-80 hours after end of infusion, D8 and D15 pre-and post-infusion; C2: D1 pre- and post-infusion; C4: D1 pre- and post-infusion; C6: D1 pre- and post-infusion; C8: D1 pre- and post-infusion (cycle length = 21 days) Serum samples for assessment of obinutuzumab serum concentrations were collected only from a subset of Japanese participants following administration of 1000 mg obinutuzumab.
Trial Locations
- Locations (235)
Humber River Hospital
🇨🇦Toronto, Ontario, Canada
UCLA - School of Medicine; Division of Hematology/Oncology
🇺🇸Los Angeles, California, United States
Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
🇵🇱Gdansk, Poland
Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
🇵🇱Lublin, Poland
Hospital Universitari Sant Joan de Reus; Servicio de Oncologia
🇪🇸Reus, Tarragona, Spain
Medical University of Lodz; Hematology
🇵🇱Lodz, Poland
Institute of Hematology
🇷🇸Belgrade, Serbia
National Cancer Inst.
🇹🇭Bangkok, Thailand
Siriraj Hospital; Division of Hematology, Department of Medicine
🇹🇭Bangkok, Thailand
Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre
🇲🇽Chihuahua, Mexico
A.O. Universitaria S. Martino Di Genova; Ematologia 1
🇮🇹Genova, Liguria, Italy
Centro Hemato Oncologico Panama
🇵🇦Panama, Panama
National Oncology Inst. ; Dept. of Haematology
🇸🇰Bratislava, Slovakia
Kantonsspital Graubünden;Onkologie und Hämatologie
🇨🇭Chur, Switzerland
Ramathibodi Hospital; Division of Hematology, Department of Medicine
🇹🇭Bangkok, Thailand
Medical Uni of Wroclaw; Hematology
🇵🇱Wroclaw, Poland
Clinical Center Vojvodine; Clinic for Hematology
🇷🇸Novi Sad, Serbia
Mecklenburg Medical Group Charlotte
🇺🇸Charlotte, North Carolina, United States
Ironwood Cancer TX & Rsch Ctrs
🇺🇸Chandler, Arizona, United States
MD Anderson Cancer Center Department of Lymphoma & Myeloma
🇺🇸Houston, Texas, United States
Monash Medical Centre; Haematology
🇦🇺Melbourne, Victoria, Australia
Joliet Oncology-Hematology; Associates, Ltd.
🇺🇸Joliet, Illinois, United States
Central Georgia Cancer Care PC
🇺🇸Macon, Georgia, United States
Sanatorio Parque de Rosario
🇦🇷Rosario, Argentina
Mercy Oncology / Hematology Center; Oncology
🇺🇸Portland, Maine, United States
Cleveland CL N Coast Cancer Cr
🇺🇸Sandusky, Ohio, United States
The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
🇨🇳Beijing, China
Texas Oncology, Pa - Amarillo
🇺🇸Amarillo, Texas, United States
Illinois Cancer Care, P.C. - Galesburg
🇺🇸Galesburg, Illinois, United States
Frankston Hospital; Oncology/Haematology
🇦🇺Frankston, Victoria, Australia
Sanatorio Britanico: Hematologia
🇦🇷Rosario, Argentina
Peking University First Hospital
🇨🇳Beijing, China
Beijing Hospital of Ministry of Health; Hematology
🇨🇳Beijing, China
Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stammz
🇩🇪Aachen, Germany
Friedrich-Alexander-Universität Erlangen-Nürnberg; Medizinische Klinik V
🇩🇪Erlangen, Germany
Fundacion Cardioinfantil
🇨🇴Bogota, Colombia
Organizacion Sanitas Internacional
🇨🇴Bogota, Colombia
Saskatoon Cancer Centre; Uni of Saskatoon Campus
🇨🇦Saskatoon, Saskatchewan, Canada
Hopital de L'Enfant-Jesus; Hematology
🇨🇦Quebec City, Quebec, Canada
Cancer Hospital Chinese Academy of Medical Sciences.
🇨🇳Beijing, China
Fn Hr. Kralove; IV. Interni Hematologicka Klinika
🇨🇿Hradec Kralove, Czechia
Ospedale "A.Tortora" - Ematologia; Dipartimento Di Ematologia
🇮🇹Pagani (Sa), Campania, Italy
The First Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, China
The Second Affiliated Hospital to Nanchang University
🇨🇳Nanchang, China
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia
🇮🇹Reggio Emilia, Emilia-Romagna, Italy
Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia
🇮🇹Milano, Lombardia, Italy
National Institute of Oncology, A Dept of Internal Medicine
🇭🇺Budapest, Hungary
General Hospital of Chinese PLA; Department of Hematology
🇨🇳Beijing, China
Petz Aladar Megyei Korhaz; Hematologia
🇭🇺Gyor, Hungary
Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
🇩🇪Heidelberg, Germany
Beijing Cancer Hospital
🇨🇳Beijing, China
Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
🇮🇹Napoli, Campania, Italy
Onkologische Schwerpunktpraxis Kurfürstendamm
🇩🇪Berlin, Germany
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
🇮🇹Brescia, Lombardia, Italy
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
🇮🇹Alessandria, Piemonte, Italy
Az. Osp. S. Luigi Gonzaga; S.C.D.U. Medicina Interna Ii
🇮🇹Orbassano, Piemonte, Italy
Kaposi Mor Teaching Hospital, Dept of Internal Medicine/Hematology
🇭🇺Kaposvar, Hungary
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I
🇩🇪Dresden, Germany
University of Szeged, II Dept of Internal Medicine
🇭🇺Szeged, Hungary
Mary Potter Oncology Centre
🇿🇦Groenkloof, South Africa
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
🇮🇹Bologna, Emilia-Romagna, Italy
Osaka City University Hospital; Hematology
🇯🇵Osaka, Japan
Ospedale Riuniti; Divisione Di Ematologia
🇮🇹Reggio Calabria, Calabria, Italy
Iwate Medical University Hospital;Hematology and Oncology
🇯🇵Iwate, Japan
Hospital San Raffaele
🇮🇹Milano, Lombardia, Italy
Toranomon Hospital; Hematology
🇯🇵Tokyo, Japan
Yonsei University Severance Hospital; Medical Oncology
🇰🇷Seoul, Korea, Republic of
Kurume University Hospital; Hematology and Oncology
🇯🇵Fukuoka, Japan
Niigata Cancer Center Hospital; Internal Medicine
🇯🇵Niigata, Japan
Nippon Medical School Hospital; Hematology
🇯🇵Tokyo, Japan
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
🇪🇸Barcelona, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
Az. Osp. S. Maria; Dept. Di Oncologia Medica
🇮🇹Terni, Umbria, Italy
Aarhus Universitetshospital, Hæmatologisk Afdeling R
🇩🇰Århus, Denmark
Rigshospitalet; Hæmatologisk Klinik
🇩🇰København Ø, Denmark
Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium
🇩🇰Roskilde, Denmark
the First Hospital of Jilin University
🇨🇳Changchun, China
Hu Nan Provincial Cancer Hospital
🇨🇳Changsha, China
Fujian Medical University Union Hospital
🇨🇳Fujian, China
Guangdong General Hospital
🇨🇳Guangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, China
First Hospital of China Medical University
🇨🇳Shenyang, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
🇨🇳Wuhan, China
The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)
🇨🇳Xi'an, China
Irccs Policlinico San Matteo; Divisione Di Ematologia
🇮🇹Pavia, Lombardia, Italy
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
🇮🇹Torino, Piemonte, Italy
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
🇮🇹Torino, Piemonte, Italy
Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
🇮🇹Bari, Puglia, Italy
Ospedale Ca Foncello; Ematologia
🇮🇹Treviso, Veneto, Italy
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Tom Baker Cancer Centre; Dept of Medicine
🇨🇦Calgary, Alberta, Canada
North York General Hospital
🇨🇦Toronto, Ontario, Canada
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
🇨🇦Toronto, Ontario, Canada
Chum Hopital Notre Dame; Centre D'Oncologie
🇨🇦Montreal, Quebec, Canada
Mcgill University - Royal Victoria Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Rocky Mountain Cancer Center - Aurora
🇺🇸Aurora, Colorado, United States
cCare
🇺🇸Encinitas, California, United States
Semmelweis University, First Dept of Medicine
🇭🇺Budapest, Hungary
Centre de sante et de services sociaux Rimouski Neigette
🇨🇦Rimouski, Quebec, Canada
Arizona Oncology
🇺🇸Tucson, Arizona, United States
California Cancer Associates for Research & Excellence, Inc.
🇺🇸Encinitas, California, United States
Florida Cancer Specialists; Department of Oncology
🇺🇸Fort Myers, Florida, United States
Cancer Care & Hematology; Specialists of Chicagoland
🇺🇸Niles, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Florida Cancer Specialists; Saint Petersburg
🇺🇸Saint Petersburg, Florida, United States
Park Nicollet Clin-Cancer Ctr
🇺🇸Saint Louis Park, Minnesota, United States
Minnesota Oncology Hematology Woodbury
🇺🇸Woodbury, Minnesota, United States
Medical University of SC (MUSC)
🇺🇸Charleston, South Carolina, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Signal Point Clinical; Research Center, LLC
🇺🇸Middletown, Ohio, United States
Willamette Valley Cancer Insitute and Research Center
🇺🇸Springfield, Oregon, United States
South Carolina Oncology Associates - SCRI
🇺🇸Columbia, South Carolina, United States
Chattanooga Oncology and Hematology Associates, PC
🇺🇸Chattanooga, Tennessee, United States
Tennessee Onc., PLLC - SCRI
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Fort Worth 12th Ave
🇺🇸Fort Worth, Texas, United States
Cancer Care Centers of South Texas-HOAST - San Antonio
🇺🇸New Braunfels, Texas, United States
Virginia Cancer Specialists - Winchester
🇺🇸Winchester, Virginia, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Instituto Damic
🇦🇷Cordoba, Argentina
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Wenatchee Valley Hospital & Clinics
🇺🇸Wenatchee, Washington, United States
Cairns Base Hospital; Cancer Care Centre
🇦🇺Cairns, Queensland, Australia
Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie
🇦🇹Innsbruck, Austria
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
🇦🇹Salzburg, Austria
Hospital Mae de Deus
🇧🇷Porto Alegre, RS, Brazil
Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie
🇦🇹Wien, Austria
Instituto de Ensino e Pesquisa Sao Lucas - IEP
🇧🇷Sao Paulo, SP, Brazil
Centro de Pesquisas Oncologicas - CEPON
🇧🇷Florianopolis, SC, Brazil
Hospital Santa Marcelina;Oncologia
🇧🇷Sao Paulo, SP, Brazil
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Queen Elizabeth II Health Sciences Centre; Oncology
🇨🇦Halifax, Nova Scotia, Canada
Ottawa General Hospital
🇨🇦Ottawa, Ontario, Canada
Hopital Maisonneuve- Rosemont; Oncology
🇨🇦Montreal, Quebec, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou, China
The First Affiliate Hospital of Guangxi Medical University
🇨🇳Nanning, China
Changhai Hospital of Shanghai
🇨🇳Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
🇨🇿Brno, Czechia
First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
FOSCAL
🇨🇴Floridablanca, Colombia
Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center
🇨🇳Wuhan, China
Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
🇨🇿Praha 2, Czechia
Klinik der Justus-Liebig-Universität; Innere Medizin
🇩🇪Gießen, Germany
Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie
🇩🇪Würzburg, Germany
University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B
🇭🇺Debrecen, Hungary
University of Pecs, I st Dept of Internal Medicine
🇭🇺Pecs, Hungary
Nuovo Policlinico, Ii Facolta; Divisione Di Ematologia
🇮🇹Napoli, Campania, Italy
A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica
🇮🇹Udine, Friuli-Venezia Giulia, Italy
Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico
🇮🇹Milano, Lombardia, Italy
Ospedali Riuniti del Canavese
🇮🇹Ivrea, Piemonte, Italy
Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
🇮🇹Novara, Piemonte, Italy
IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo
🇮🇹San Giovanni Rotondo, Puglia, Italy
Azienda Ospedaliero Univ
🇮🇹Catania, Sicilia, Italy
Az. Osp. C. Panico; Rep. Ematologia E Trapianto
🇮🇹Tricase - LE, Puglia, Italy
Az. Osp. Papardo; Struttura Complessa Di Ematologia
🇮🇹Messina, Sicilia, Italy
Azienda Ospedaliera Univ
🇮🇹Firenze, Toscana, Italy
Uni Di Verona Policlinico G.B. Rossi; Divisione E Cattedra Di Ematologia
🇮🇹Verona, Veneto, Italy
Ospedale Di Vicenza; Nefrologia, Ematologia
🇮🇹Vicenza, Veneto, Italy
Chiba University Hospital; Hematology
🇯🇵Chiba, Japan
Ospedale Santa Chiara; Unita Operativa Di Ematologia
🇮🇹Pisa, Toscana, Italy
Nagoya Daini Red Cross Hospital; Hematology & Oncology
🇯🇵Aichi, Japan
Kyushu University Hospital; Hematology, Oncology & Cardiovascular medicine
🇯🇵Fukuoka, Japan
Gifu University Hospital; First Department of Internal Medicine
🇯🇵Gifu, Japan
Shimane University Hospital;Hematology
🇯🇵Shimane, Japan
Hokkaido University Hospital; Hematology
🇯🇵Hokkaido, Japan
Kobe City Medical Center General Hospital; Hematology
🇯🇵Hyogo, Japan
Yokohama City University Hospital; Hematology, Rheumatology, Infectious Disease
🇯🇵Kanagawa, Japan
Kyoto University Hospital; Department of Hematology/Oncology
🇯🇵Kyoto, Japan
Osaka University Hospital; Hematology and Oncology
🇯🇵Osaka, Japan
Kurashiki Central Hospital; Hematology
🇯🇵Okayama, Japan
National Cancer Center Hospital; Hematology
🇯🇵Tokyo, Japan
Kindai University Hospital; Hematology and Rheumatology
🇯🇵Osaka, Japan
Jichi Medical University Hospital; Hematology
🇯🇵Tochigi, Japan
The Cancer Institute Hospital of JFCR; Hematology Oncology
🇯🇵Tokyo, Japan
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Asan Medical Center - Oncology
🇰🇷Seoul, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
St. Mary'S Hospital, the Catholic University School of Medicine; Internal Medicine
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Dr. Jose E. Gonzalez; Haematology
🇲🇽Monterrey, Mexico
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Oaxaca Site Management Organization
🇲🇽Oaxaca, Mexico
Instituto;Oncologico Miraflores
🇵🇪Lima, Peru
Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny
🇵🇱Brzozów, Poland
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
Clinica de Especialidades Medicas
🇵🇪Lima, Peru
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
🇵🇱Warszawa, Poland
Republican Clinical Hospital n.a. Baranov; Haematology
🇷🇺Petrozavodsk, Russian Federation
Clinical Oncology Dispensary of Ministry of Health of Tatarstan
🇷🇺Kazan, Russian Federation
Regional Clinical Hospital N.A. Semashko; Hematology
🇷🇺Nizhny Novgorod, Russian Federation
Blokhin Cancer Research Center; Clinical Oncology
🇷🇺Moscow, Russian Federation
Penza Regional Oncology Dispensary
🇷🇺Penza, Russian Federation
Research Inst. of Hematology & Blood Transfusion ; Hematology
🇷🇺St Petersburg, Russian Federation
Constantiaberg Medical Clinic; Dept. of Haematology & Bone Marrow Translant
🇿🇦Cape Town, South Africa
Medical Oncology Centre of Rosebank; Oncology
🇿🇦Johannesburg, South Africa
Drs Thomson, Brittain an Partners Inc
🇿🇦Pretoria, South Africa
Wits Donald Gordon Clinical Trial Centre; Medical Oncology
🇿🇦Parktown, Johannesburg, South Africa
Hospital de Navarra, Servicio de Hematología
🇪🇸Pamplona, Navarra, Spain
Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia
🇪🇸Toledo, Spain
Hospital del Mar; Servicio de Hematologia
🇪🇸Barcelona, Spain
Hospital Duran i Reynals; Servicio de Hematologia
🇪🇸Barcelona, Spain
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal; Servicio de Hematologia
🇪🇸Madrid, Spain
Complejo Hospitalario de Pontevedra; Servicio de Oncologia
🇪🇸Pontevedra, Spain
Kantonsspital Aarau; Zentrum Für Onkologie, Hämatologie & Transfusionsmedizin
🇨🇭Aarau, Switzerland
Ospedale San Giovanni; Oncologia
🇨🇭Bellinzona, Switzerland
Veterans General Hospital; Division of Oncology
🇨🇳Taipei, Taiwan
National Taiwan Universtiy Hospital; Division of Hematology
🇨🇳Taipei, Taiwan
Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
🇨🇳Taoyuan, Taiwan
King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine
🇹🇭Bangkok, Thailand
Birmingham Heartlands Hospital; Department of Haematology
🇬🇧Birmingham, United Kingdom
Rajavithi Hospital; Medicine
🇹🇭Bangkok, Thailand
Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine
🇹🇭Khon Kaen, Thailand
Aberdeen Royal Infirmary; Haematology - Ward 16
🇬🇧Aberdeen, United Kingdom
Addenbrookes Hospital; Haematology
🇬🇧Cambridge, United Kingdom
The HOPE Clinical Trials Unit
🇬🇧Leicester, United Kingdom
New Cross Hospital; Dept. Of Haematology
🇬🇧Wolverhampton, United Kingdom
Forsyth Regional Cancer Center; Piedmont Hematology/Oncology Associates
🇺🇸Winston-Salem, North Carolina, United States
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
🇮🇹Roma, Lazio, Italy
Centro de Estudios Clinicos de Queretaro, SC
🇲🇽Queretaro, Mexico
UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
🇨🇭Zürich, Switzerland
Jiangsu Province Hospital
🇨🇳Nanjing, China
Queen Mary Hospital; Dept of Medicine
🇭🇰Hong Kong, Hong Kong
Pamela Youde Nethersole Eastern Hospital; Department of Medicine
🇭🇰Hong Kong, Hong Kong
Fujian Cancer Hospital
🇨🇳Fuzhou, China