Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs

Phase 3

Completed

Conditions: Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes

Interventions: Drug: Guadecitabine
Other: Treatment Choice

Registration Number: NCT02907359

Lead Sponsor: Astex Pharmaceuticals, Inc.

Brief Summary: A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in participants with MDS or CMML who failed or relapsed after adequate prior treatment with azacitidine, decitabine, or both. This global study will be conducted in approximately 15 countries. Approximately 408 participants from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 participants) or Treatment Choice (approximately 136 participants). The study consists of a 21-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last more than 2 years, and the duration of individual participant participation will vary. Participants may continue to receive treatment for as long as they continue to benefit.

Detailed Description: Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment Choice (TC). Approximately 408 participants will be randomly assigned 2:1 to either guadecitabine or TC.

* Guadecitabine: approximately 272 participants.

* TC: approximately 136 participants.

Before randomization, the investigator will assign each participant to one of the following TC options:

* Low dose cytarabine (LDAC).

* Standard Intensive Chemotherapy (IC) of a 7+3 regimen.

* Best Supportive Care (BSC) only. BSC will be provided to all participants as per standard and institutional practice. Participants randomized to TC will not be allowed to cross over to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at regular intervals, primarily to evaluate safety during study conduct. Randomization will be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts \>10% vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region.

Guadecitabine: 60 milligrams per square meter (mg/m\^2) given subcutaneously (SC) daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond 6 cycles, treatment should continue as long as the participant continues to benefit. BSC should be given according to standard and institutional practice.

Treatment Choice (TC): Before randomization, the investigator will assign each participant to one of the following TC options:

* Low dose cytarabine (LDAC) given as 20 mg/m\^2 SC or intravenously (IV) once daily for 14 days in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 4 cycles in the absence of disease progression or unacceptable toxicity.

* Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200 mg/m\^2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m\^2/day), or idarubicin (9-12 mg/m\^2/day), or mitoxantrone (8-12 mg/m\^2/day) by intravenous infusion for 3 days.

* Best Supportive Care (BSC) only: given according to standard and institutional practice. BSC includes, but is not limited to blood transfusions (Red blood cells \[RBCs\] or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad-spectrum antibiotics and/or antifungals.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 417

Inclusion Criteria

Adult participants ≥18 years of age who are able to understand and comply with study procedures and provide written informed consent before any study-specific procedure.
Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.
Performance status (ECOG) of 0-2.
Previously treated MDS or CMML, defined as prior treatment with at least one hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high risk MDS or CMML whose disease progressed or relapsed as follows:
1. Participant received HMA for at least 6 cycles and was still transfusion dependent.
2. Participant received HMA for at least 2 complete cycles and had disease progression prior to Cycle 6 defined as
i. ≥50% increase in bone marrow blasts from pre-HMA-treatment levels or from nadir post-HMA-treatment levels to >5% (for participants with pretreatment or nadir blasts ≤5%) or to >10% (for participants with pretreatment or nadir blasts >5%), and/or ii. Transfusion dependent and ≥2 gram/deciliter (g/dL) reduction of Hgb from pre-HMA-treatment levels.

Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed.

Participants must have either:
1. Bone marrow blasts >5% at randomization, OR
2. Transfusion dependence, defined as having had transfusion (in the setting of active disease) of 2 or more units of RBC or platelets within 8 weeks prior to randomization.
Creatinine clearance or glomerular filtration rate ≥30 milliliter/minute (mL/min) estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment with guadecitabine and for at least 3 months after completing treatment and (b) while receiving treatment with LDAC or IC and for at least 6 months after completing treatment or for the duration specified in local prescribing information, whichever is longer.

Exclusion Criteria

Participants who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20%.
Participants who may still be sensitive to repeated treatment with decitabine or azacitidine such as participants who had response to prior decitabine or azacitidine treatment, but relapsed >6 months after stopping treatment with these agents.
Prior treatment with guadecitabine.
Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
Treated with any investigational drug within 2 weeks of the first dose of study treatment.
Total serum bilirubin >2.5 × upper limit of normal (ULN) (except for participants with Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C.
Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol.
Refractory congestive heart failure unresponsive to medical treatment, active infection resistant to all antibiotics, or advanced non-MDS associated pulmonary disease requiring >2 liters per minute oxygen.
Life expectancy of less than one month
Participants with TP53 mutations

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Guadecitabine	Guadecitabine	Participants received Guadecitabine 60 mg/m\^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
Treatment Choice	Treatment Choice	Participants received one of the three treatment choice options: 1. LDAC 20 mg/m\^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. 2. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m\^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m\^2) by IV infusion for 3 days of each 28-day cycles. 3. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization up to death (up to approximately 38.6 months)	OS was defined as the number of days from the day the participant was randomized to the date of death due to any cause. Survival time was censored on the last date the participant is known alive with no event of death. OS time will be estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Transfusion Independence for Any 8 Consecutive Weeks	Up to approximately 46.6 months	Transfusion independence rate was calculated as the number of participants with neither RBC nor platelet transfusion for any period of 8 weeks after the initiation of treatment (or cycle 1 day 1 { C1D1} visit date for participants randomized to BSC or randomization date for participants not treated) and up to treatment discontinuation (or 180 days for participants discontinuing the treatment within 6 months), while maintaining haemoglobin (Hgb) ≥8 gram per deciliter (g/dL) and platelets ≥20×10\^9/liter (L) divided by the total number of participants included in the efficacy analysis. RBC or Platelet transfusion independence rate was defined similarly as above. Percentage of participants are rounded off to the single decimal point.
Leukemia-free Survival	From randomization up to 46.6 months	Leukemia-free survival was defined as the number of days from randomization to the earliest date when participants have bone marrow (BM) or peripheral blood (PB) blasts ≥20%, conversion to acute myeloid leukemia (AML) or death of any cause. Participants with no events in leukemia-free survival were censored on the last date of BM or PB blasts assessment, whichever is later. Survival time will be estimated using the Kaplan-Meier method.
Disease Response (DR) Rate	Up to approximately 46.6 months	DR: Complete Response(CR), Partial Response(PR),Marrow Complete Response(mCR), and Hematological Improvement(HI) including HI with Erythroid (HI-E), HI with Neutrophil (HI-N), or HI with Platelet (HI-P) based on IWG 2006 criteria. CR: BM:≤5% myeloblasts, Peripheral blood: Hgb≥11g/dL, Platelets(PLTs)≥100x10\^9/L, Neutrophils≥1.0x10\^9/L, Blasts 0%. PR: All CR criteria if abnormal before treatment except BM blasts decreased ≥50% over pretreatment but still\>5%, Cellularity, morphology not relevant. HI responses:1) HI-E: Hgb increase ≥1.5g/dL, Relevant reduction of RBC units transfusions by absolute ≥4 RBC transfusions/8 week(wk) compared with pretreatment transfusion number previous 8wk. Only RBC transfusions given for Hgb≤9.0g/dL. 2) HI-P: Absolute increase≥30x10\^9/L starting\>20x10\^9/L PLTs; Increase from\<20x10\^9/L to\>20x10\^9/L and by≥100%. 3) HI-N: ≥100% increase, absolute increase\>0.5x10\^9/L.
Survival Rate at 1 Year After Randomization	From randomization up to 12 months	One year survival rate was defined as the percentage of participants that survived at the end of the first year from randomization. Participants who did not have death in record were censored on the last date known to be alive. Percentage of participants are rounded off to the nearest whole number.
Number of Red Blood Cell (RBC) and Platelet Transfusions	Up to 6 months	The total number of RBCs transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit. The mean total number of RBC or platelet units transfused per participant is presented.
Percentage of Participants With Marrow Complete Response (mCR) Along With Transfusion Independence Rate	Up to approximately 46.6 months	mCR was defined as per 2006 Myelodysplastic Syndromes International Council for Harmonisation (MDS IWG) criteria as reduction of bone marrow (BM) blasts to ≤5% and decrease by 50% or more with or without normalization of peripheral counts. Transfusion independence rate was calculated as the number of participants with neither RBC nor platelet transfusion for any period of 8 weeks after the initiation of treatment (or C1D1 visit date for participants randomized to BSC or randomization date for participants not treated) and up to treatment discontinuation (or 180 days for participants discontinuing the treatment within 6 months), while maintaining Hgb ≥8 g/dL and platelets ≥20×10\^9/L divided by the total number of participants included in the efficacy analysis. The percentage of participants who achieved mCR and transfusion independence simultaneously in the same period were calculated for each group. Percentage of participants are rounded off to the single decimal point.
Number of Days Alive and Out of the Hospital (NDAOH)	Up to 6 months	The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The NDAOH within first 6 month period was calculated as: NDAOH 6M=180 -total duration of all hospital stays within 180 days from the first treatment -number of death days before Day 180. For participants who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the participant would have died the day after the last contact day.
Duration of Complete Response (CR)	Up to approximately 46.6 months	Duration of complete response (in number of days) was calculated from the first time a CR was observed to the date of the earliest of the following three events: 1) relapse/disease progression, 2) start of alternative therapy (except Hematopoietic Cell Transplant \[HCT\]) or 3) death. In the absence of any event, the duration of CR was censored at the last available time point (BM assessment, PB assessment, or safety/long-term follow-up visit) at which an event was not observed. Duration of complete response was analysed using a Kaplan-Meier method for participants who achieved a CR during the study. CR: BM: ≤5% myeloblasts (all cell lines normal maturation), Peripheral blood: Hgb ≥11g/dL, PLTs ≥100x10\^9/L, Neutrophils ≥1.0x10\^9/L, Blasts 0%.
Time to First Response, Complete Response (CR) and Best Response	From study Day 1 to the earliest date that a response was first documented (up to approximately 46.6 months)	Time to first response was the time(days) from randomization to first date when any response was achieved. Time to CR was the time(days) from randomization to first date when CR was achieved. Time to best response was the time(days) from randomization to first date when participant's best response (CR,PR,mCR or HI) was achieved. CR:BM:≤5% myeloblasts, Peripheral blood:Hgb≥11g/dL,PLTs≥100x10\^9/L,Neutrophils≥1.0x10\^9/L,Blasts 0%. PR: All CR criteria except BM blasts decreased≥50% over pretreatment but still \>5%,Cellularity,morphology not relevant. mCR: Reduction of BM blasts to≤5%; decrease ≥50% with/without normalization of peripheral counts. HI responses:1)HI-E:Hgb increase≥1.5 g/dL, Relevant reduction of RBC units transfusions by absolute≥4 RBC transfusions/8wk compared with pretreatment transfusion number previous 8wk. 2)HI-P:Absolute increase≥30x10\^9/L starting\>20x10\^9/L PLTs; Increase from≤20 to\>20x10\^9/L and by≥100% 3)HI-N:≥100% granulocyte increase, absolute increase\>0.5x10\^9/L.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From first dose through end of study (up to approximately 46.6 months)	An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization; results in persistent or significant disability; is congenital anomaly; is suspected transmission of any infectious agent via a medicinal product or is medically important. Treatment emergent AEs which are those with onset date on or after the date of the first dose of study drug on C1D1 until 30 days after the last dose of study treatment, or the start of an alternative anticancer treatment, whichever occurs first.
Change From Baseline in Health-related Quality of Life (QOL) By EuroQol 5-level 5-dimension (EQ-5D-5L) Summary Index	Baseline to Month 6	The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L, first component is a descriptive system five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a second component visual analogue scale (VAS) that measures health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. The health status is converted to an index value using the country-specific weighted scoring algorithm for England. The summary index value for the England ranges from a worst score of -0.281 to a best score of 1. An increase in the EQ-5D-5L total score indicates improvement.
Change From Baseline in Health-related QOL: EuroQOL Visual Analogue Scale (EQ-VAS) Score	Baseline to Month 6	The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. The second component, EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine).
30-day and 60-day All-cause Mortality	From first dose until 60 days after study treatment initiation	Number of deaths, regardless of cause, within 30 or 60 days from the first study dose divided by the total number of participants included in the Safety Analysis Set. Participants who died within 30 days were also included in the 60-day mortality calculations.

Trial Locations

Locations (112): Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Swedish Cancer Institute
🇺🇸
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
Duke Cancer Center
🇺🇸
Durham, North Carolina, United States
Odense University Hospital
🇩🇰
Odense, Denmark
Desert Hematology Oncology Medical Group, Inc.
🇺🇸
Rancho Mirage, California, United States
Franciscan Health Indianapolis
🇺🇸
Indianapolis, Indiana, United States
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
Bon Secours Saint Francis Hospital
🇺🇸
Greenville, South Carolina, United States
Burnaby Hospital
🇨🇦
Burnaby, Canada
Maisonneuve-Rosemont Hôpital Service d'Hematologie et d'Oncologie Medicale
🇨🇦
Montréal, Canada
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Aarhus Universitetshospital
🇩🇰
Aarhus, Denmark
GHR Mulhouse Sud-Alsace
🇫🇷
Mulhouse Cedex, France
Fakultni Nemocnice Hradec Králové
🇨🇿
Hradec Králové, Czechia
Saskatchewan Cancer Agency
🇨🇦
Regina, Canada
Fakultní nemocnice Brno
🇨🇿
Brno, Czechia
Aalborg Universitetshospital
🇩🇰
Aalborg, Denmark
Hôpital Hôtel-Dieu
🇫🇷
Nantes, France
University of Fukui Hospital
🇯🇵
Yoshida, Fukui, Japan
Centre Antoine Lacassagne
🇫🇷
Nice, France
Chugoku Central Hospital
🇯🇵
Fukuyama-shi, Hiroshima, Japan
Marien Hospital Düsseldorf
🇩🇪
Düsseldorf, Germany
Fakultní nemocnice Ostrava
🇨🇿
Ostrava, Czechia
Tom Baker Cancer Center
🇨🇦
Calgary, Alberta, Canada
Onkologická klinika Všeobecná fakultní nemocnice v Praze a 1
🇨🇿
Praha 2, Czechia
Fakultní Nemocnice Královské Vinohrady
🇨🇿
Praha, Czechia
Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
🇮🇹
Alessandria, Italy
Hôpital Saint Louis
🇫🇷
Paris, France
Centre Hospitalier Universitaire de Toulouse
🇫🇷
Toulouse, France
Azienda Ospedaliero Universitaria Careggi
🇮🇹
Firenze, Italy
Centre Hospitalier Lyon Sud
🇫🇷
Pierre-Bénite, France
AORN A. Cardarelli
🇮🇹
Napoli, Italy
Universitaetsklinikum Freiburg
🇩🇪
Freiburg, Germany
Universitätsklinikum Ulm
🇩🇪
Ulm, Germany
Städtisches Klinikum Braunschweig
🇩🇪
Braunschweig, Germany
Narita Red Cross Hospital
🇯🇵
Narita, Chiba, Japan
Universitätsklinikum Halle
🇩🇪
Halle, Germany
Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara
🇮🇹
Novara, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
Ospedale S. Eugenio
🇮🇹
Roma, Italy
Nagasaki University Hospital
🇯🇵
Nagasaki, Nagasaki-shi, Japan
Fundació Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Japanese Red Cross Kyoto Daini Hospital
🇯🇵
Kyoto, Japan
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Spain
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱
Lublin, Poland
Ulsan University Hospital
🇰🇷
Ulsan, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Instytut Hematologii i Transfuzjologii
🇵🇱
Warszawa, Poland
Yamagata University Hospital
🇯🇵
Yamagata, Japan
Hospital General Universitario de Alicante
🇪🇸
Alicante, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸
Madrid, Spain
Hospital de León
🇪🇸
León, Spain
Hospital San Pedro de Alcantara
🇪🇸
Cáceres, Spain
Hospital Universitario de Salamanca
🇪🇸
Salamanca, Spain
Hospital Universitario Ramón Y Cajal
🇪🇸
Madrid, Spain
Sahlgrenska Universitetssjukhuset, Östra sjukhuset
🇸🇪
Göteborg, Sweden
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
The Leeds Teaching Hospitals NHS Trust
🇬🇧
Leeds, United Kingdom
Kitasato University Hospital
🇯🇵
Sagamihara-shi, Kanagawa, Japan
Yokohama Municipal Citizen's Hospital
🇯🇵
Yokohama, Kanagawa, Japan
Gifu Municipal Hospital
🇯🇵
Gifu, Japan
Fukushima Medical University
🇯🇵
Fukushima, Japan
Saitama Medical Center
🇯🇵
Kawagoe, Saitama, Japan
National Hospital Organization Kumamoto Medical Center
🇯🇵
Kumamoto, Japan
Nottingham University Hospitals NHS Trust
🇬🇧
Nottingham, United Kingdom
Hospital Universitari Germans Trias i Pujol
🇪🇸
Badalona, Spain
Weill Cornell Medical College
🇺🇸
New York, New York, United States
University of Michigan Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
City of Hope
🇺🇸
Duarte, California, United States
Mount Sinai Medical Center
🇺🇸
Miami Beach, Florida, United States
Cancer Specialists of North Florida
🇺🇸
Fleming Island, Florida, United States
North Shore Medical Center
🇺🇸
Evanston, Illinois, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
John Theurer Cancer Center
🇺🇸
Hackensack, New Jersey, United States
Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
Moncton Hospital
🇨🇦
Moncton, Canada
Ziekenhuis Netwerk Antwerpen Stuivenberg
🇧🇪
Antwerp, Belgium
West Virginia University Mary Babb Randolph Cancer Center
🇺🇸
Morgantown, West Virginia, United States
Royal Victoria Regional Health Centre
🇨🇦
Barrie, Ontario, Canada
Juravinski Cancer Centre
🇨🇦
Hamilton, Ontario, Canada
Rigshospitalet
🇩🇰
Copenhagen, Denmark
Centre Hospitalier Universitaire
🇫🇷
La Tronche, France
Hôpital Dupuytren
🇫🇷
Limoges, France
Azienda Ospedaliera Universitaria San Martino
🇮🇹
Genova, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
🇮🇹
Pesaro, Italy
NHO Nagoya Medical Center
🇯🇵
Nagoya-shi, Aichi, Japan
Tokai University Hospital
🇯🇵
Isehara, Kanagawa, Japan
National Hospital Organization Disaster Medical Center
🇯🇵
Tachikawa, Tokyo, Japan
Kansai Medical University Hirakata
🇯🇵
Hirakata, Osaka, Japan
National Hospital Organization Kyushu
🇯🇵
Fukuoka, Japan
Kindai University Hospital
🇯🇵
Osakasayama-shi, Osaka, Japan
University Hospital-Kyoto Prefectural University of Medicine
🇯🇵
Kyoto, Japan
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Seoul Saint Mary's Hospital
🇰🇷
Seoul, Korea, Republic of
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Medway NHS Foundation Trust
🇬🇧
Gillingham, United Kingdom
Penn State Milton S. Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
🇯🇵
Koto, Tokyo, Japan
NTT Medical Center Tokyo
🇯🇵
Shinagawa, Tokyo, Japan
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende
🇧🇪
Brugge, Belgium
Grand Hôpital de Charleroi - Notre Dame
🇧🇪
Charleroi, Belgium
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱
Warszawa, Poland
Nippon Medical School Hospital
🇯🇵
Bunkyō-Ku, Tokyo, Japan
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Chelsea and Westminster Hospital NHS Foundation Trust
🇬🇧
London, United Kingdom
Universitetssjukhuset Örebro
🇸🇪
Örebro, Sweden