Study Comparing Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care Chemotherapy for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia
- Conditions
- Newly Diagnosed Philadelphia (Ph)-Negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL)
- Interventions
- Registration Number
- NCT04994717
- Lead Sponsor
- Amgen
- Brief Summary
The safety run-in part of the study aims to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The phase 3 part of the study aims to compare event-free survival (EFS) and overall survival (OS) of participants receiving blinatumomab alternating with low-intensity chemotherapy to EFS and (OS) of participants receiving standard of care (SOC) chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 284
- Age ≥ 55 years at the time of informed consent. OR
Age 40 to < 55 years of age if at least 1 of the following comorbidities at the time of informed consent:
-
history of grades 3 and 4 pancreatitis
-
diabetes mellitus with end-organ damage
-
severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and aspartate transaminase (AST)/alanine aminotransferase (ALT) > 10 x upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy)
-
body mass index (BMI) ≥ 40 combined with relevant comorbidities such as metabolic syndrome
-
Any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric based, adult adapted standard chemotherapy regimen but still compatible with the suggested protocol for older participants in both the experimental and the SOC arm. The participant history will be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed.
- Participants with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOG score allowed if due to underlying leukemia
- All participants must have adequate organ function as defined below:
-
renal: estimated glomerular filtration rate based on MDRD calculation ≥ 50 mL/min/1.73 m^2
-
liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert's Disease or if liver involvement with leukemia); exception for participants 40 to < 55 years of age if they have a comorbidity listed above: severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and AST/ALT > 10 x ULN (liver cirrhosis must be confirmed by biopsy)
-
cardiac: left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, myocardial infarction or stroke within 3 months). Consult with medical monitor as needed.
-
Active central nervous system (CNS) leukemia (i.e., CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening.
-
History of other malignancy within the past 3 years, with the following exceptions:
- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Adequately treated breast ductal carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
- Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
-
Clinically relevant CNS pathology or event such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric conditions that preclude the use of high dose of corticosteroids
-
Current autoimmune disease or history of autoimmune disease with potential CNS involvement
-
Known infection with human immunodeficiency virus (HIV)
-
Known infection with chronic or active infection with hepatitis B (eg, hepatitis b surface [HBs] antigen reactive or quantifiable hepatitis b virus [HBV] viral load) or hepatitis C virus (HCV) (eg, HCV RNA [qualitative] is detected).
Active hepatitis B and C based on the following results:
-
positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
-
negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCR result is necessary to enroll.
-
positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCR result is necessary to enroll.
- Participant with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection.
- Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or optional pre-phase (debulking) chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 3: Standard of care (SOC) chemotherapy SOC chemotherapy regimen Participants will receive 1 of 2 SOC chemotherapy regimens (GMALL or HyperCVAD) per investigator's choice. Phase 3: Blinatumomab alternating with low-intensity chemotherapy Blinatumomab Participants will receive blinatumomab alternating with low-intensity chemotherapy. Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy Blinatumomab The safety run-in will be performed prior to initiating the phase 3 randomized part of the study. This safety run-in is to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The safety run-in also evaluates a shorter dose step interval from (4 days instead of 7 days) and a 1-week (instead of 2-week) drug free interval between blinatumomab cycles. Blinatumomab will be infused at a lower dose for 4 days and increase to a higher dose on Day 5 of the infusion for the remainder of the infusion. Phase 3: Blinatumomab alternating with low-intensity chemotherapy Low-intensity chemotherapy regimen Participants will receive blinatumomab alternating with low-intensity chemotherapy. Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy Low-intensity chemotherapy regimen The safety run-in will be performed prior to initiating the phase 3 randomized part of the study. This safety run-in is to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The safety run-in also evaluates a shorter dose step interval from (4 days instead of 7 days) and a 1-week (instead of 2-week) drug free interval between blinatumomab cycles. Blinatumomab will be infused at a lower dose for 4 days and increase to a higher dose on Day 5 of the infusion for the remainder of the infusion.
- Primary Outcome Measures
Name Time Method Phase 3: Event-free Survival (EFS) Up to approximately 5 years Time from randomization (enrollment) until treatment failure, relapse or death from any cause, whichever is earlier.
Treatment failure is defined as not achieving a hematological complete CR with MRD response \<10-4 by the end of the initial disease assessment period.
Relapse is defined as hematologic relapse, extramedullary relapse, and/or molecular relapse (MRD positivity \>= 10\^-3), whichever occurs earlier, in participants with prior achievement of hematologic CR with MRD response \<10\^-4.
Participants without an event will be censored at their last evaluable disease assessment date.Safety run-in: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) Up to approximately 5 years Number and percentage of participants who experience one or more TEAE, serious TEAE, treatment-related adverse events, and adverse events of interest.
Phase 3: Overall Survival (OS) Up to approximately 5 years OS is defined as time from randomization (enrollment) until death due to any cause.
- Secondary Outcome Measures
Name Time Method Safety run-in: Complete Remission (CR) Rate by the End of Initial Disease Assessment Period Baseline to Week 14 Safety run-in: Minimal Residual Disease (MRD) Response by the End of Initial Disease Assessment Period Baseline to Week 14 MRD response is defined as the percentage of participants who achieve a response of \< 10\^-4 measured by polymerase chain reaction (PCR).
Safety run-in: Clearance (CL) of Blinatumomab Up to approximately 34 weeks Safety run-in: Relapse-free Survival (RFS) Up to approximately 5 years RFS: In participants who achieve CR, the time from first achievement of this response until date of the first relapse including hematologic relapse, extramedullary relapse, or death due to any cause, whichever occurs first.
Safety run-in: Minimal Residual Disease (MRD) Relapse Free Survival (RFS) Up to approximately 5 years MRD RFS: In participants who achieve CR with MRD response, the time from first achievement of this response until date of of the first relapse including molecular relapse, hematological relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. (Molecular relapse will be defined 2 ways: MRD\>= 10\^-3 and MRD\>=10\^-4. Participants without an event will be censored at their last evaluable disease assessment date.
Safety run-in: Steady State Concentration (Css) of Blinatumomab Up to approximately 34 weeks Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Fatigue Score Baseline to Week 14 Fatigue score will be measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - Short Form 7a.
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Pain Score Baseline to Week 14 Pain score will be measured by Brief Pain Inventory - Short Form (BPI-SF); Item 3: pain at its worst in the last 24 hours.
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Global Health Status Baseline to Week 14 Global health status will be measured by the Quality of Life Questionnaire (QLQ)-C30 global health status quality of life scale.
Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Physical Function Baseline to Week 14 Physical function will be measured by the QLQ-C30 functional scale.
Phase 3: Complete Remission (CR) Rate by the End of Initial Disease Assessment Period Baseline to Week 14 Phase 3: Change from Baseline to End of Initial Disease Assessment Period in Nausea and Vomiting Baseline to Week 14 Nausea and vomiting will be measured by the QLQ-C30 symptom scale.
Phase 3: Minimal Residual Disease (MRD) Response by the End of Initial Disease Assessment Period Baseline to Week 14 MRD response is defined as the percentage of participants who achieve a response of \< 10\^4 measured by polymerase chain reaction (PCR).
Phase 3: Relapse-free Survival (RFS) Up to approximately 5 years RFS: In participants who achieve CR, the time from first achievement of this response until the date of the first relapse including hematologic relapse, extra medullary relapse, or death due to any cause, whichever occurs first. Participants without an event will be censored at their last evaluable disease assessment date.
Phase 3: Minimal Residual Disease (MRD) Relapse Free Survival (RFS) Up to approximately 5 years In participants who achieve CR with MRD response, the time from first achievement of this response until date of the first relapse including molecular relapse, hematologic relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. Molecular relapse will be defined 2 ways: MRD\>= 10\^-3 and MRD\>= 10\^-4. Participants without an event will be censored at their last evaluable disease assessment date
Phase 3: Minimal Residual Disease (MRD) Over Time Up to approximately 5 years Phase 3: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) Up to approximately 5 years Number and percentage of participants who experience one or more TEAE, serious TEAE, treatment-related adverse events, and adverse events of interest.
Phase 3: Number of Participants who Experience Cluster of Differentiation (CD) 19 Positive and Negative Relapse by Flow Cytometry for Bone Marrow Up to approximately 5 years Phase 3: Number of Participants who Experience Cluster of Differentiation (CD) 19 Positive and Negative Relapse Identified by Immunohistochemistry or Flow Cytometry for Cerebrospinal Fluid Up to end of safety follow up (approximately 44 months) Phase 3: Number of Participants who Experience Cluster of Differentiation (CD) 19 Positive and Negative Relapse for Extramedullary Sites other than Cerebrospinal Fluid Up to end of safety follow up (approximately 44 months) Phase 3: Rate of Lineage Switch to Acute Myeloid Leukemia (AML) Up to end of safety follow up (approximately 44 months) Phase 3: Localization of Relapse by Clinical Assessment Up to end of safety follow up (approximately 44 months) Phase 3: Mortality Rate in Participants who Experience Complete Remission (CR) Up to approximately 5 years Phase 3: Number of Participants who have Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT) in Participants who Experience Continuous First Complete Remission (CR) Up to approximately 5 years Phase 3: Mortality Rate in Participants who Experience Complete Remission (CR) after Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) Up to approximately 5 years Phase 3: Relapse Rate Following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) Up to approximately 5 years Phase 3: Time to Deterioration using the Fatigue Score Up to approximately 5 years Fatigue score will be measured by PROMIS Fatigue-Short Form 7a.
Phase 3: Time to Improvements using the Fatigue Score Up to approximately 5 years Fatigue score will be measured by PROMIS Fatigue-Short Form 7a.
Phase 3: Time to Deterioration using the Pain Score Up to approximately 5 years Pain score will be measured by BPI-SF; Item 3: pain at its worst in the last 24 hours.
Phase 3: Time to Improvements using the Pain Score Up to approximately 5 years Pain score will be measured by BPI-SF; Item 3: pain at its worst in the last 24 hours.
Phase 3: Change from Baseline in Global Health Status, Physical Function, Nausea/Vomiting, and All Other Subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Baseline to end of study (up to approximately 5 years) EORTC QLQ-C30 will include global health status, physical functioning, emotional functioning, cognitive functioning, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties will be measured by EORTC QLQ-C30.
Phase 3: Time to Deterioration for Global Health Status, Physical Function, Nausea/Vomiting, and All Other Subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Up to approximately 5 years Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties will be measured by EORTC QCQ-C30.
Phase 3: Time to Improvements for Global Health Status, Physical Function, Nausea/Vomiting, and All Other Subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Up to approximately 5 years Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties will be measured by EORTC QCQ-C30.
Steady State Concentration of Blinatumomab Up to approximately Day 36 Clearance of Blinatumomab Up to approximately Day 36
Trial Locations
- Locations (168)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California Irvine
🇺🇸Orange, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Adventist Health System/Sunbelt, Inc d/b/a AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Saint Francis Hospital, Inc
🇺🇸Greenville, South Carolina, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Brisbane and Womens Hospital
🇦🇺Herston, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Austin Health, Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Medizinische Universitaet Graz
🇦🇹Graz, Austria
Medizinische Universitaet Innsbruck
🇦🇹Innsbruck, Austria
Ordensklinikum Linz Elisabethinen
🇦🇹Linz, Austria
Hanusch Krankenhaus
🇦🇹Wien, Austria
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
AZ Sint-Jan Brugge-Oostende AV
🇧🇪Brugge, Belgium
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent
🇧🇪Ghent, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
🇧🇪Hasselt, Belgium
Centre Hospitalier Universitaire de Liege - Sart Tilman
🇧🇪Liege, Belgium
AZ Delta Campus Rumbeke
🇧🇪Roeselare, Belgium
Centre Hospitalier Universitaire Dinant Godinne - Universite Catholique de Louvain Namur
🇧🇪Yvoir, Belgium
Hospital das Clinicas de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Fundacao Amaral Carvalho
🇧🇷Jau, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira Icesp
🇧🇷São Paulo, Brazil
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
🇧🇬Plovdiv, Bulgaria
Specialized Hospital for Active Treatment of Hematology Diseases EAD
🇧🇬Sofia, Bulgaria
Arthur J E Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Queen Elizabeth II, Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Hamilton Health Sciences - Juravinski Hospital and Cancer Centre
🇨🇦Hamilton, Ontario, Canada
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
CEMTL Hopital Maisonneuve Rosemont
🇨🇦Montreal, Quebec, Canada
Fundacion Arturo Lopez Perez
🇨🇱Santiago, Chile
Inmunocel
🇨🇱Santiago, Chile
Clinica Alemana de Santiago
🇨🇱Santiago, Chile
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Aarhus Universitetshospital
🇩🇰Aarhus N, Denmark
Rigshospitalet
🇩🇰København Ø, Denmark
Odense Universitetshospital
🇩🇰Odense, Denmark
Helsinki University Hospital
🇫🇮Helsinki, Finland
Turku University Hospital
🇫🇮Turku, Finland
Hopital Henri Mondor
🇫🇷Creteil, France
Centre Hospitalier Universitaire de Dijon - Hopital du Bocage
🇫🇷Dijon, France
Centre Hospitalier de Versailles - Hopital Andre Mignot
🇫🇷Le Chesnay Cedex, France
Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Hospitalier Universitaire de Nantes - Hopital Hotel Dieu
🇫🇷Nantes, France
Centre Hospitalier Universitaire Archet 2
🇫🇷Nice cedex 3, France
Hopital Saint Louis
🇫🇷Paris, France
Hopital Saint Antoine
🇫🇷Paris, France
Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque
🇫🇷Pessac Cedex, France
Hopital Lyon Sud
🇫🇷Pierre Benite, France
Centre Hospitalier Universitaire de Rennes
🇫🇷Rennes Cedex 9, France
Institut Universitaire du Cancer Toulouse Oncopole
🇫🇷Toulouse cedex 9, France
Centre Hospitalier Universitaire de Nancy - Hopital de Brabois
🇫🇷Vandoeuvre les Nancy Cedex, France
Universitaetsklinikum Augsburg
🇩🇪Augsburg, Germany
Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
🇩🇪Berlin, Germany
Universitaetsklinikum Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Duesseldorf
🇩🇪Duesseldorf, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Universitaetsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Klinikum der LMU Muenchen
🇩🇪Muenchen, Germany
Evangelismos Hospital
🇬🇷Athens, Greece
Laiko General Hospital of Athens
🇬🇷Athens, Greece
Attiko General University Hospital
🇬🇷Athens, Greece
University Hospital of Heraklion
🇬🇷Heraklion, Greece
University Hospital of Ioannina
🇬🇷Ioannina, Greece
University Hospital of Larissa
🇬🇷Larissa, Greece
University Hospital of Patras
🇬🇷Patras, Greece
General Hospital of Thessaloniki Georgios Papanikolaou
🇬🇷Thessaloniki, Greece
Queen Mary Hospital, The University of Hong Kong
🇭🇰Hong Kong, Hong Kong
Princess Margaret Hospital
🇭🇰Kowloon, Hong Kong
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
🇭🇺Budapest, Hungary
Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia
🇮🇹Perugia, Italy
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet
🇭🇺Eger, Hungary
Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz Nyiregyhazi Josa Andras Tagkorhaz
🇭🇺Nyiregyhaza, Hungary
Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari
🇮🇹Bari, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni xxiii
🇮🇹Bergamo, Italy
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola
🇮🇹Bologna, Italy
Ospedale Policlinico San Martino IRCCS
🇮🇹Genova, Italy
Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
🇮🇹Lecce, Italy
Azienda Unità Locale Socio Sanitaria 3 Ospedale Dell Angelo
🇮🇹Mestre (VE), Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli
🇮🇹Napoli, Italy
Azienda Unita Sanitaria Locale Pescara Ospedale Civile Santo Spirito
🇮🇹Pescara, Italy
Azienda Ospedaliera Policlinico Umberto I
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria Integrata di Verona Ospedale G B Rossi Borgo Roma
🇮🇹Verona, Italy
Nagoya University Hospital
🇯🇵Nagoya-shi, Aichi, Japan
Akita University Hospital
🇯🇵Akita-shi, Akita, Japan
Tesshokai Kameda General Hospital
🇯🇵Kamogawa-shi, Chiba, Japan
University of Fukui Hospital
🇯🇵Yoshida-gun, Fukui, Japan
Kyushu University Hospital
🇯🇵Fukuoka-shi, Fukuoka, Japan
Kurume University Hospital
🇯🇵Kurume-shi, Fukuoka, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima-shi, Fukushima, Japan
Gunma Saiseikai Maebashi Hospital
🇯🇵Maebashi-shi, Gunma, Japan
Sapporo Hokuyu Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe-shi, Hyogo, Japan
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Ishikawa, Japan
Tokai University Hospital
🇯🇵Isehara-shi, Kanagawa, Japan
Yokohama City University Medical Center
🇯🇵Yokohama-shi, Kanagawa, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Nagasaki, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama-shi, Okayama, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka-shi, Osaka, Japan
Kindai University Hospital
🇯🇵Osakasayama-shi, Osaka, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-shi, Tochigi, Japan
Nihon University Itabashi Hospital
🇯🇵Itabashi-ku, Tokyo, Japan
Yamagata University Hospital
🇯🇵Yamagata-shi, Yamagata, Japan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Boca Clinical Trials Mexico SC
🇲🇽Ciudad de Mexico, Distrito Federal, Mexico
Centro Oncologico Internacional
🇲🇽Mexico City, Distrito Federal, Mexico
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo León, Mexico
Hematologica Alta Especialidad
🇲🇽Huixquilucan, Mexico
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Unidade Local de Saude de Coimbra, EPE
🇵🇹Coimbra, Portugal
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE
🇵🇹Lisboa, Portugal
Unidade Local de Saude de Sao Jose, EPE - Hospital de Santo Antonio dos Capuchos
🇵🇹Lisboa, Portugal
Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
🇵🇹Porto, Portugal
Institutul Clinic Fundeni
🇷🇴Bucharest, Romania
Institutul Oncologic Prof Dr Ion Chiricuta
🇷🇴Cluj-Napoca, Romania
Institutul Regional de Oncologie Iasi
🇷🇴Iasi, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
🇷🇴Sibiu, Romania
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Andalucía, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Andalucía, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Complejo Asistencial Universitario de Salamanca Hospital Universitario de Salamanca
🇪🇸Salamanca, Castilla León, Spain
Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Cataluña, Spain
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Cataluña, Spain
Institut Catala d Oncologia Hospitalet Hospital Duran i Reynals
🇪🇸Hospitalet de Llobregat, Cataluña, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Comunidad Valenciana, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Goteborg, Sweden
Inselspital Bern
🇨🇭Bern, Switzerland
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
🇨🇳Taoyuan, Taiwan
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷Ankara, Turkey
Ankara Bilkent Sehir Hastanesi
🇹🇷Ankara, Turkey
Memorial Antalya Hastanesi
🇹🇷Antalya, Turkey
Bagcilar Medipol Mega Universite Hastanesi
🇹🇷Istanbul, Turkey
Dokuz Eylul Universitesi Tip Fakultesi Hastanesi
🇹🇷Izmir, Turkey
Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
🇹🇷Samsun, Turkey
University College London
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom