A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)
- Conditions
- Post-polycythemia Vera MyelofibrosisPost-essential Thrombocythemia MyelofibrosisPrimary Myelofibrosis
- Interventions
- Registration Number
- NCT04173494
- Lead Sponsor
- Sierra Oncology LLC - a GSK company
- Brief Summary
MOMENTUM is a randomized, double-blind, active control Phase 3 trial intended to confirm the differentiated clinical benefits of the investigational drug momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic participants who have previously received an approved Janus kinase inhibitor (JAKi) therapy for myelofibrosis (MF). The purpose of this clinical study is to compare the effectiveness and safety of MMB to DAN in treating and reducing: 1) disease related symptoms, 2) the need for blood transfusions and 3) splenomegaly, in adults with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The study is planned in countries including, but not limited to: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom (UK) and United States (US).
Participants must be symptomatic with a Myelofibrosis Symptom Assessment Form (MFSAF) version (v) 4.0 Total Symptom Score of \>= 10 at screening, and be anemic with hemoglobin (Hgb) \< 10 gram/deciliter (g/dL). For participants with ongoing JAKi therapy at screening, JAKi therapy must be tapered over a period of at least 1 week, followed by a 2-week non-treatment washout interval prior to randomization.
Participants will be randomized 2:1 to orally self-administer blinded treatment: MMB plus placebo or DAN plus placebo. Participants randomized to receive MMB who complete the randomized treatment period to the end of Week 24 may continue to receive MMB in the open-label extended treatment period to the end of Week 204 (a total period of treatment of approximately 4 years) if the participants tolerates and continues to benefit from MMB.
Participants randomized to receive DAN may cross-over to MMB open-label treatment in the following circumstances: at the end of Week 24 if they complete the randomized treatment period; or at the end of Week 24 if they discontinue treatment with DAN but continue study assessments and do not receive prohibited medications including alternative active anti-MF therapy; or at any time during the randomized treatment period if they meet the protocol-defined criteria for radiographically confirmed symptomatic splenic progression. Participants randomized to receive DAN who are receiving clinical benefit at the end of Week 24 may choose to continue DAN therapy up to Week 48. The comparator treatment, DAN, is an approved medication in the US and in some other countries and is recommended by national guidelines as a treatment for anemia in MF.
- Detailed Description
MOMENTUM Contact Email: GSKClinicalSupportHD@gsk.com
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
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Age >= 18 years.
-
Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post- polycythemia vera/essential thrombocythemia (PV/ET) MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria).
-
Symptomatic, defined as a TSS of >= 10 units assessed by a single MFSAF v4.0 assessment during Screening prior to Baseline period (Day BL1).
-
Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period.
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Previously treated with an approved JAK inhibitor for PMF or Post-PV/ET MF for >= 90 days, or >= 28 days if JAK inhibitor therapy is complicated by RBC transfusion requirement of >= 4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma.
-
Baseline splenomegaly, defined as having a palpable spleen at >= 5 centimeter (cm), below the left costal margin, or with volume >= 450 cubic centimeter (cm^3) on imaging (ultrasound, magnetic resonance imaging [MRI] or computed tomography [CT] are acceptable), assessed during Screening at any point prior to Randomization.
-
High risk, intermediate-2, or intermediate-1 risk MF as defined by Dynamic International Prognostic Scoring System (DIPSS), or DIPSS-plus.
-
No allogeneic stem cell transplant planned.
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Acceptable laboratory assessments:
- Absolute neutrophil count (ANC) >= 0.75 × 10^9/Liter (L).
- Platelet count (PLT) >= 25 × 10^9/L (without requirement for platelet transfusion).
- Peripheral blast count < 10%.
- Alanine aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) <= 3 × Upper Limit Normal (ULN) (<= 5 × ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days).
- Calculated creatinine clearance (CCr) >= 30 milliliter per minute (mL/min) according to Cockcroft-Gault.
- Direct bilirubin <= 2.0 × ULN.
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Use of the following treatments within the time periods noted:
- Prior momelotinib treatment at any time.
- Approved JAK inhibitor therapy (eg, fedratinib or ruxolitinib) within 1 week prior to the first day of Baseline.
- Active anti-MF therapy within 1 week prior to the first day of Baseline.
- Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization.
- Investigational agent (including investigational JAK inhibitors) within 4 weeks prior to Randomization.
- Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
- Danazol within 3 months prior to Randomization.
- Splenic irradiation within 3 months prior to Randomization.
- Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin.
-
History of prostate cancer, with the exception of localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured.
-
Prostate specific antigen (PSA) > 4 nanograms per milliliter (ng/mL).
-
Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI scan or CT scan for spleen volume measurement per protocol requirements.
-
Any of the following (criteria a - k):
- Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial).
- Significant active or chronic bleeding event >= Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
- Unstable angina pectoris within 6 months prior to Randomization.
- Symptomatic congestive heart failure within 6 months prior to Randomization.
- Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
- QT Interval Corrected Using Fridericia's Formula (QTcF) interval > 500 millisecond (msec), unless attributed to bundle branch block.
- Current progressive thrombosis despite treatment.
- History of porphyria.
- Child-Pugh score >= 10.
- Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor.
- Inability or unwillingness to comply with the protocol restrictions on MF therapy and other medications prior to and during study treatment.
-
Participants with a prior or concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efficacy assessment of the investigational regimen.
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Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or thalassemia.
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Known positive status for human immunodeficiency viruses (HIV).
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Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C).
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Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0.
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Presence of peripheral neuropathy >= Grade 2 per CTCAE v5.0.
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Women who are already pregnant or lactating. Additional inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Momelotinib Placebo to match danazol Participants will receive momelotinib plus placebo to match danazol Danazol Placebo to match momelotinib Participants will receive danazol plus placebo to match momelotinib Momelotinib Momelotinib Participants will receive momelotinib plus placebo to match danazol Danazol Danazol Participants will receive danazol plus placebo to match momelotinib
- Primary Outcome Measures
Name Time Method Total Symptom Score (TSS) Response Rate at Week 24 Baseline and Week 24 Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a \>= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.
- Secondary Outcome Measures
Name Time Method Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- up to Week 24 Up to Week 24 An adverse event (AE) is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Percentage of Participants With Transfusion Independence (TI) at Week 24 Week 24 TI status was defined as not receiving red blood cell (RBC) or whole blood transfusion for \>=12 weeks, with no hemoglobin (Hgb) level \< 8 grams per deciliter (g/dL) during the same interval. Percentage of participants with TI have been presented.
Splenic Response Rate (SRR) of >=25% at Week 24 Baseline and Week 24 Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of \>=25% from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
Duration of MFSAF TSS Response Up to a maximum of 151 weeks Duration of MFSAF TSS response is defined as the number of days from the start of the initial 28-day period in which a participant had a \>= 50% reduction from Baseline TSS to the first day of the 7-day assessment that determines the mean TSS for the 28-day period during which the participants TSS equals or exceeds their Baseline value.
Duration of TI in Baseline TD Participants Up to a maximum of 151 weeks Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level \< 8 g/dL (except in the case of clinically overt bleeding).
Change From Baseline in Physical Function Score as Assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b at Week 24 Baseline and Week 24 PROMIS Physical Function Short Form 10b consists of 14 questions; each with a 5-point response. PROMIS short form assesses self-reported capability of a participant rather than actual performance of physical activities. This includes functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) as well as instrumental activities of daily living, such as running errands. Participants scored each response on a scale from 1 (unable to do) to 5 (without any difficulty, or not at all). Total possible range of scores was 14 to 70, with higher scores corresponding to a greater physical function ability. An increase in score from Baseline indicated an improvement in physical function ability and a decrease in score from Baseline indicated a reduction in physical function ability. Baseline was last assessment done before or on the day of first dose date. Change from Baseline was defined as post-Baseline value minus Baseline value.
Splenic Response Rate (SRR) of >= 35% at Week 24 Baseline and Week 24 Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of \>=35 % from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
Duration of TI Response Up to a maximum of 151 weeks Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level \< 8 g/dL (except in the case of clinically overt bleeding).
Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- From Week 24 to a Maximum of 151 Weeks From Week 24 to a maximum of 151 weeks An AE is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Overall Survival (OS) Up to a maximum of 151 weeks Overall survival is defined as the interval from the first study drug dosing date (or randomization date for participants who did not receive treatment) to death from any cause.
Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks Up to 24 weeks Percentage of participants with zero RBC units transfused over 24-weeks were reported.
Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks Up to 24 weeks Percentage of participants with \<=4 RBC units transfused over 24-weeks were reported.
Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks Up to Week 24 Cumulative transfusion risk was calculated as the estimated mean cumulative number of whole blood units transfused during the study.
Change From Baseline in MFSAF TSS at Week 24 Baseline and Week 24 TSS was measured using the MFSAF v4.0. The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). The MFSAF TSS was calculated as the sum of scores of the 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Percentage of Participants With Transfusion Dependence (TD) Status at Week 24 Week 24 TD status at Week 24 is defined as requirement of \>=4 RBC units in an 8-week period immediately prior to the end of Week 24.
Percentage of Participants With a Hemoglobin Response Baseline and Week 24 Hemoglobin responses are defined as increases of \>= 1, \>= 1.5, or \>= 2 g/dL from Baseline in Hgb, as measured over a (rolling) period of at least 12 consecutive weeks falling entirely before the end of Week 24. Baseline was the last assessment done before or on the day of first dose date. Data has been reported for percentage of participants who had \>= 1, \>= 1.5, or \>= 2 g/dL increase from Baseline in hemoglobin.
Number of Baseline TD Participants With TI Status at Week 24 Week 24 Participants were defined as having TD if they met both of the following requirements in the 8 weeks immediately before the end of Week 24: \>= 4 red blood cell or whole blood units were transfused (except in the case of clinically overt bleeding), each in response to a hemoglobin assessment of \<= 9.5 g/dL; and there were \>= 2 hemoglobin assessments with \>= 28 days between the earliest and latest hemoglobin assessments. TI status was defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for \>= 12 weeks immediately prior to the end of Week 24, with hemoglobin levels \>= 8 g/dL.
Leukemia-free Survival (LFS) Up to a maximum of 151 weeks LFS is defined as the interval from first study drug dosing date (or randomization date for participants who did not receive treatment) to any evidence of leukemic transformation and/or death (from any cause).
Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at Week 24 Baseline and Week 24 The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant- and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Data has been reported for Disease-related Fatigue domain measured using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable), higher score indicates worst outcome. An increase in score from Baseline indicated a worsening of fatigue and a decrease in score from Baseline indicated an improvement in fatigue. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Change From Baseline in Cancer-related Fatigue as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at Week 24 Baseline and Week 24 The EORTC QLQ-C30 is comprised of 5 functional scales (physical, role, emotional, social, cognitive), eight single item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea), as well as sub-scales assessing global health/quality of life and financial impact. Most items use a 4-point Likert scale from "not at all" to "very much" and a one-week recall period with the exception of the final two items which use a 7 point scale response from "very poor" to "excellent". Scores were averaged and transformed to a 0-100 scale, with higher scores representing better functioning/quality of life. An increase in scores from Baseline indicated an improved functioning/quality of life, and a decrease in scores from Baseline indicated a worsened functioning/quality of life. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Trial Locations
- Locations (167)
Irvine Center for Clinical Research
🇺🇸Irvine, California, United States
Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Guy's and Saint Thomas' NHS Foundation Trust
🇬🇧London, England, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, England, United Kingdom
Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Instytut Hematologii I Transfuzjologii
🇵🇱Warszawa, Mazowieckie, Poland
Laboratul clinic MedLife-Policlinica de Diagnostic Rapid Brasov
🇷🇴Braşov, Romania
Singapore General Hospital
🇸🇬Singapore, Singapore
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
National Specialized Hospital for Active Treatment of Haematologic Diseases
🇧🇬Sofia, Bulgaria
McMaster University Medical Center
🇨🇦Hamilton, Ontario, Canada
Azienda Ospedaliero - Universitaria Careggi
🇮🇹Firenze, Florence, Italy
Oberösterreichische Gesundheitsholding GmbH
🇦🇹Steyr, Austria
Hôpital De La Conception
🇫🇷Marseille, France
Yitzhak Shamir Medical Center
🇮🇱Be'er Ya'aqov, Central District, Israel
Perth Radiological Clinic - Magnetic Resonance Centre
🇦🇺Perth, Western Australia, Australia
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Aalborg Universitetshospital - Syd
🇩🇰Aalborg, Nordjylland, Denmark
Grand Hôpital de Charleroi - Notre Dame
🇧🇪Charleroi, Hainaut, Belgium
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Canberra Region Cancer Centre
🇦🇺Garran, Australian Capital Territory, Australia
Hôpital Erasme
🇧🇪Bruxelles, Brussels, Belgium
Ziekenhuis Netwerk Antwerpen Stuivenberg
🇧🇪Antwerpen, Belgium
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Belgium
Queen Elizabeth II Health Sciences Centre - Halifax Infirmary
🇨🇦Halifax, Nova Scotia, Canada
Saint Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Ordensklinikum Linz Elisabethinen
🇦🇹Linz, Upper Austria, Austria
University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
🇧🇬Pleven, Bulgaria
Pécsi Tudományegyetem Klinikai Központ
🇭🇺Pécs, Baranya, Hungary
Hadassah University Hospital Ein Kerem
🇮🇱Jerusalem, Jerusalem District, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
University Hospital St. Ivan Rilski
🇧🇬Sofia, Bulgaria
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Somogy, Hungary
Szabolcs-Szatmár-Bereg Megyei Kórházak És Egyetemi Oktatókórház
🇭🇺Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary
Western Galilee Hospital-Nahariya
🇮🇱Nahariya, Israel
Klinika Hematologii Nowotworów Krwi i Transplantacji Szpiku
🇵🇱Wrocław, Dolnoslaskie, Poland
Silesian Healthy Blood Clinic
🇵🇱Chorzów, Salskie, Poland
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Hôpital Claude Huriez
🇫🇷Lille, Hauts-de-France, France
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Research Institute of the McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Rambam Health Care Campus
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Markusovszky Egyetemi Oktatókórház Szombathely
🇭🇺Szombathely, Vas, Hungary
Petz Aladár Megyei Oktató Kórház
🇭🇺Győr, Hungary
Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Lubelskie, Poland
Szpital Wojewódzki w Opolu
🇵🇱Opole, Opolskie, Poland
Alvamed Zakład Specjalistycznej Opieki Zdrowotnej
🇵🇱Warszawa, Mazowieckie, Poland
Szpital Uniwersytecki w Krakowie
🇵🇱Kraków, Malopolskie, Poland
Chang Gung Memorial Hospital - Linkou Branch
🇨🇳Taoyuan, Taiwan
University College London Hospitals NHS Foundation Trust
🇬🇧London, England, United Kingdom
Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
🇵🇱Łódź, Poland
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Spitalul Filantropia - Craiova
🇷🇴Craiova, Dolj, Romania
Institutul Regional De Oncologie Iasi
🇷🇴Iaşi, Iasi County, Romania
China Medical University Hospital
🇨🇳Taichung City, Taichung, Taiwan
University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, England, United Kingdom
American Institute of Research - Whittier
🇺🇸Whittier, California, United States
Washington University School of Medicine in Saint Louis
🇺🇸Saint Louis, Missouri, United States
Northwest Oncology & Hematology - Rolling Meadows
🇺🇸Rolling Meadows, Illinois, United States
Columbia University Irving Medical Center - Presbyterian Hospital
🇺🇸New York, New York, United States
Cleveland Clinic - Richard E. Jacobs Health Center
🇺🇸Avon, Ohio, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Calvary Mater Newcastle Hospital
🇦🇺Waratah, New South Wales, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
🇧🇪Brugge, West-Vlaanderen, Belgium
University Multiprofile Hospital For Active Treatment Aleksandrovska
🇧🇬Sofia, Bulgaria
Herlev Hospital
🇩🇰Herlev, Hovedstaden, Denmark
Sjællands Universitetshospital - Roskilde
🇩🇰Roskilde, Sjælland, Denmark
Fakultni Nemocnice Brno
🇨🇿Brno, Jihormoravsky Kraj, Czechia
Hôpital de l'Enfant-Jésus
🇨🇦Québec, Canada
Odense Universitetshospital
🇩🇰Odense, Syddanmark, Denmark
Hospital Center University Of Caen Normandie
🇫🇷Caen, Basse-Normandie, France
Hôpital Saint-Louis
🇫🇷Paris, Ile-de-France, France
Centre Hospitalier Universitaire Limoges
🇫🇷Limoges, Limousin, France
Hôpital Haut-Lévêque
🇫🇷Pessac, Aquitaine, France
Hôpital Saint-Antoine
🇫🇷Paris, Ile-de-France, France
Centre Hospitalier De Lens
🇫🇷Lens, Nord Pas-Des-Calais, France
Centre Hospitalier Universitaire Amiens-Picardie - Site Sud
🇫🇷Amiens, Picardie, France
Centre Hospitalier Le Mans
🇫🇷Le Mans, Pays De La Loire, France
Hôpital l'Archet
🇫🇷Nice, Provence-Alpes-Côte d'Azur, France
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Bénite, Rhone-Alps, France
Centre Hosptitalier Universitaire Angers
🇫🇷Angers, France
Hôpital Saint-Vincent De Paul - Lille
🇫🇷Lille, France
Hôpital Emile Muller
🇫🇷Mulhouse, France
Centre Hospitalier Universitaire Nantes - Hôtel Dieu
🇫🇷Nantes, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
Universitätsklinikum Aachen
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Nordrhein-Westfalen, Germany
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Sachsen, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Universitätsklinikum Halle
🇩🇪Halle, Sachsen-Anhalt, Germany
Universitätsklinikum Jena
🇩🇪Jena, Thuringen, Germany
Uniklinik Köln
🇩🇪Köln, Germany
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
🇩🇪Lübeck, Germany
Kliniken Ostalb - Stauferklinikum Schwäbisch Gmünd
🇩🇪Mutlangen, Germany
Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet - Szent László Telephely
🇭🇺Budapest, Pest, Hungary
Szent Borbála Kórház
🇭🇺Tatabánya, Komárom-Esztergom, Hungary
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hajdu-Bihar, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Bnai Zion Medical Center
🇮🇱Haifa, Haifa District, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Forli-Cesena, Italy
Rabin Medical Center - Beilinson Hospital
🇮🇱Petah tikva, Israel
Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo
🇮🇹Monza, Monza E Brianza, Italy
IRCCS Centro di Riferimento Oncologico di Basilicata
🇮🇹Rionero In Vulture, Potenza, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
🇮🇹Pesaro, Pesaro E Urbino, Italy
Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
🇮🇹Torino, Turin, Italy
Azienda Ospedaliera Ordine Mauriziano di Torino
🇮🇹Torino, Turin, Italy
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo - Alessandria
🇮🇹Alessandria, Italy
Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
🇮🇹Bologna, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
🇮🇹Novara, Italy
Umberto I - Policlinico di Roma
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Presidio Ospedaliero Universitario Santa Maria della Misericordia
🇮🇹Udine, Italy
Ospedale Policlinico Giambattista Rossi Borgo Roma
🇮🇹Verona, Italy
Kyungpook National University Hospital
🇰🇷Daegu, Daegu Gwang'yeogsi, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
North Shore Hospital
🇳🇿Auckland, New Zealand
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Middlemore Clinical Trials
🇳🇿Auckland, New Zealand
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
🇵🇱Kraków, Małopolskie, Poland
Uniwersyteckie Centrum Kliniczne w Gdańsku
🇵🇱Gdańsk, Pomorskie, Poland
Spitalul Clinic Judetean De Urgenta Târgu Mureș
🇷🇴Târgu-Mureş, Mureș, Romania
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Coltea - Spital Clinic
🇷🇴Bucharest, Romania
Institut Hospital del Mar d'Investigacions Mèdiques
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital San Pedro de Alcantara
🇪🇸Cáceres, Spain
Institut Català d'Oncologia Girona
🇪🇸Girona, Spain
Complejo Asistencial Universitario de Salamanca - Hospital Clínico
🇪🇸Salamanca, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Karolinska Universitetssjukhuset Solna
🇸🇪Solna, Stockholm, Sweden
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital de Día Quirónsalud Zaragoza
🇪🇸Zaragoza, Spain
Uddevalla Sjukhus
🇸🇪Uddevalla, Sweden
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Västra Götalands Län, Sweden
Chiayi Chang Gung Memorial Hospital
🇨🇳Puzi City, Chaiyi, Taiwan
United Lincolnshire Hospitals NHS Trust
🇬🇧Boston, England, United Kingdom
NHS Lanarkshire
🇬🇧Airdrie, Scotland, United Kingdom
Severance Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Mayo Clinic Hospital - Phoenix
🇺🇸Phoenix, Arizona, United States
University of Colorado Hospital Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Medizinische Universität Wien
🇦🇹Wien, Vienna, Austria
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, England, United Kingdom
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Tyrol, Austria