Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD)
- Conditions
- Chronic Graft Versus Host Disease
- Interventions
- Registration Number
- NCT02959944
- Lead Sponsor
- Pharmacyclics LLC.
- Brief Summary
To evaluate the safety and efficacy of ibrutinib in combination with prednisone in subjects with newly diagnosed moderate to severe cGVHD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 193
- New onset moderate or severe cGVHD as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project Criteria
- Need for systemic treatment with corticosteroids for cGVHD
- No previous systemic treatment for cGVHD (including extracorporeal photopheresis [ECP])
- Participants may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d
- Age ≥12 years old
- Karnofsky or Lansky (subjects <16 years) performance status ≥60
Key
- Received any previous systemic treatment for cGVHD with the exception of corticosteroids administered for cGVHD within the 72 hours prior to signing the informed consent form.
- Inability to begin a prednisone dose ≥0.5 mg/kg/d for the treatment of cGVHD
- Any uncontrolled infection or active infection requiring ongoing systemic treatment
- Progressive underlying malignant disease or any post-transplant lymphoproliferative disease
- Known bleeding disorders
- Active hepatitis C virus (HCV) or hepatitis B virus (HBV)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Prednisone Placebo Placebo given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses. Ibrutinib + Prednisone ibrutinib Ibrutinib (420 mg) given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. The 420 mg dose was adjusted for cytochrome P450 \[CYP\] inhibitors or hepatic dysfunction as applicable. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses. Ibrutinib + Prednisone Prednisone Ibrutinib (420 mg) given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. The 420 mg dose was adjusted for cytochrome P450 \[CYP\] inhibitors or hepatic dysfunction as applicable. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses. Placebo + Prednisone Prednisone Placebo given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.
- Primary Outcome Measures
Name Time Method Primary Analysis: Response Rate at 48 Weeks 48 weeks (Cumulatively up to 30 March 2020) Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a complete response (CR) or a partial response (PR) at 48 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 48 weeks.
Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.Final Analysis: Response Rate at 48 Weeks 48 weeks (Cumulatively up to 12 July 2021) Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a complete response (CR) or a partial response (PR) at 48 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 48 weeks.
Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.
- Secondary Outcome Measures
Name Time Method Primary Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 30 March 2020) The cumulative incidence of withdrawal of all corticosteroids (95% confidence interval \[CI\]) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all corticosteroids at given time point. The time to withdrawal of corticosteroids is computed from randomization date to the first date of withdrawal of all corticosteroids for treatment of cGVHD to 0 mg daily for at least 30 days.
Primary Analysis: Response Rate at 24 Weeks 24 weeks (Cumulatively up to 30 March 2020) Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a CR or PR at 24 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 24 weeks.
Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.Final Analysis: Response Rate at 24 Weeks 24 weeks (Cumulatively up to 12 July 2021) Response rate was defined as the percentage of participants who were responders. Responders were defined as participants who had a CR or PR at 24 weeks without starting any subsequent therapy for cGVHD or having evidence of relapse of their underlying disease that was indication for transplant prior to response assessment at 24 weeks.
Response was defined using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower gastrointestinal, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR is defined as resolution of all manifestations in each organ or site. PR is defined as improvement in at least 1 organ or site without progression in any other organ or site.Final Analysis: Cumulative Incidence of Withdrawal of All Corticosteroids for Treatment of cGVHD Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021) The cumulative incidence of withdrawal of all corticosteroids (95% confidence interval \[CI\]) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all corticosteroids at given time point. The time to withdrawal of corticosteroids is computed from randomization date to the first date of withdrawal of all corticosteroids for treatment of cGVHD to 0 mg daily for at least 30 days.
Primary Analysis: Percentage of Participants Who Achieved Reduction of Prednisone Dose Level to Less Than 0.15 mg/kg/Day at 24 Weeks Sustained for at Least 30 Days 24 weeks (Cumulatively up to 30 March 2020) Primary Analysis: Overall Survival (OS) Median time on study (cumulatively up to 30 March 2020) was 19.8 months and 18.4 months for the Ibrutinib + Prednisone and Placebo + Prednisone arms, respectively. OS was defined as the time of randomization until the time of death due to any cause, in months.
Final Analysis: OS Median time on study (cumulatively up to 12 July 2021) was 33.1 months and 32.5 months for the Ibrutinib + Prednisone and Placebo + Prednisone arms, respectively. OS was defined as the time of randomization until the time of death due to any cause, in months.
Primary Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants Months 3, 6, 9, 12, 15, 18, 21, 24 (cumulatively up to 30 March 2020) The cumulative incidence of withdrawal of all immunosuppressants (95% CI) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all immunosuppressants at a given time point. The time to withdrawal of all immunosuppressants is computed from randomization date to the first date of withdrawal of all immunosuppressants for treatment of cGVHD, sustained for at least 30 days. All immunosuppressants include corticosteroids but they do not include ibrutinib.
Final Analysis: Cumulative Incidence of Withdrawal of All Immunosuppressants Months 3, 6, 9, 12, 15, 18, 21, 24 (Cumulatively up to 12 July 2021) The cumulative incidence of withdrawal of all immunosuppressants (95% CI) was calculated using SAS lifetest procedure adjusting for competing risks including death, cGVHD progression, relapse of underlying disease, and start of subsequent cGVHD therapy. Data presented are the estimated proportion of participants withdrawing all immunosuppressants at a given time point. The time to withdrawal of all immunosuppressants is computed from randomization date to the first date of withdrawal of all immunosuppressants for treatment of cGVHD, sustained for at least 30 days. All immunosuppressants include corticosteroids but they do not include ibrutinib.
Primary Analysis: Duration of Response (DOR) for Participants Who Had PR or CR at Any Time Response was assessed every 4 weeks from Week 5 through Week 25, Week 37, Week 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 30 March 2020) Response was defined using the NIH Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR was defined as resolution of all manifestations in each organ or site. PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. Duration of response was estimated by Kaplan-Meier methodology.
Primary Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits Assessed at Weeks 5, 13, 25, 37, 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 30 March 2020) Clinically meaningful improvement on Lee cGVHD symptom scale was defined as at least a 7-point decrease in Lee Symptom Scale overall summary score on at least 2 consecutive visits, not preceded by progressive disease, relapse of underlying disease or start of subsequent cGVHD treatment.
The Lee cGVHD Symptom Scale score has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely, with lower values representing a better outcome. A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. An overall score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.Final Analysis: Percentage of Participants Who Achieved Reduction of Prednisone Dose Level to Less Than 0.15 mg/kg/Day at 24 Weeks Sustained for at Least 30 Days 24 weeks (Cumulatively up to 12 July 2021) Final Analysis: Percentage of Participants With Improvement in Overall Score on Lee cGVHD Symptom Scale at Two Consecutive Visits Assessed at Weeks 5, 13, 25, 37, 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 12 July 2021) Clinically meaningful improvement on Lee cGVHD symptom scale was defined as at least a 7-point decrease in Lee Symptom Scale overall summary score on at least 2 consecutive visits, not preceded by progressive disease, relapse of underlying disease or start of subsequent cGVHD treatment.
The Lee cGVHD Symptom Scale score has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0- Not at all, 1- Slightly, 2 Moderately, 3 Quite a bit, 4-Extremely, with lower values representing a better outcome. A score is calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. An overall score is calculated as the average of these 7 subscales if at least 4 subscales have valid scores.Final Analysis: DOR for Participants Who Had PR or CR at Any Time Response was assessed every 4 weeks from Week 5 through Week 25, Week 37, Week 49, 30 days after the last dose of study drug, and then every 12 weeks of follow-up until progressed disease. (Cumulatively up to 12 July 2021) Response was defined using the NIH Consensus Panel Chronic GVHD Activity Assessment (2014). Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia are the organs or sites considered in evaluating overall response. CR was defined as resolution of all manifestations in each organ or site. PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. Duration of response was estimated by Kaplan-Meier methodology.
Primary Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone From first dose of study drug through the end of treatment plus 30 days. As of data cutoff (cumulatively up to 30 March 2020), median ibrutinib treatment duration was 5.4 months and the median placebo treatment duration was 6.4 months. AE: any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \>24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity was graded according to the Common Terminology Criteria for Adverse Events version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death). Treatment-related events are those that were possibly related or related to study treatment per investigator's judgment. Treatment emergent AEs (TEAEs) occurred from the first dose of study drug up to 30 days after the last dose of study drug.
Final Analysis: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Placebo in Combination With Prednisone From first dose of study drug through the end of treatment plus 30 days. As of data cutoff (cumulatively up to 12 July 2021), median ibrutinib treatment duration was 5.4 months and the median placebo treatment duration was 6.4 months. AE: any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \>24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity was graded according to the Common Terminology Criteria for Adverse Events version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death). Treatment-related events are those that were possibly related or related to study treatment per investigator's judgment. Treatment emergent AEs (TEAEs) occurred from the first dose of study drug up to 30 days after the last dose of study drug.
Trial Locations
- Locations (102)
Emory University, Winship Cancer Institute /ID# 1140-0033
🇺🇸Atlanta, Georgia, United States
Stanford University/Stanford Cancer Center, Pasteur Drive /ID# 1140-0400
🇺🇸Stanford, California, United States
Loyola University /ID# 1140-0713
🇺🇸Maywood, Illinois, United States
Arizona Oncology - Scottsdale - Cancer Transplant Institute Location /ID# 1140-1120
🇺🇸Scottsdale, Arizona, United States
Dr. Haunerschen Kinderspital /ID# 1140-1142
🇩🇪Munich, Germany
Centro Trapianti Cellule Staminali, Ospedale Infantile Regina Margherita /ID# 1140-1156
🇮🇹Turin, Italy
Hyogo College of Medicine College Hospital /Id# 1140-1434
🇯🇵Nishinomiya-shi, Hyogo, Japan
IRCCS Ospedale Pediatrico Bambino Gesu /ID# 1140-1150
🇮🇹Rome, Lazio, Italy
Okayama University Hospital /ID# 1140-1430
🇯🇵Okayama-shi, Okayama, Japan
Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital /ID# 1140-1437
🇯🇵Hiroshima-shi, Hiroshima, Japan
Yonsei University Health System, Severance Hospital /ID# 1140-0927
🇰🇷Seodaemun-gu, Seoul Teugbyeolsi, Korea, Republic of
Singapore General Hospital /ID# 1140-1162
🇸🇬Singapore, Singapore
SoonChunHyang University Seoul /ID# 1140-1163
🇰🇷Seoul, Korea, Republic of
Kyungpook National Univ Hosp /ID# 1140-1153
🇰🇷Daegu, Daegu Gwang Yeogsi, Korea, Republic of
China Medical University Hosp /ID# 1140-1199
🇨🇳Taichung City, Taichung, Taiwan
National Taiwan Univ Hosp /ID# 1140-1184
🇨🇳Taipei City, Taipei, Taiwan
Indiana University Melvin and Bren Simon Cancer Center /ID# 1140-0010
🇺🇸Indianapolis, Indiana, United States
Univ Hosp Cleveland /ID# 1140-0941
🇺🇸Cleveland, Ohio, United States
University of Pittsburgh - UPMC (Hillman Cancer Center) /ID# 1140-0050
🇺🇸Pittsburgh, Pennsylvania, United States
Jackson Memorial Hospital, University of Miami /ID# 1140-0647
🇺🇸Miami, Florida, United States
Boston Childrens Hospital /ID# 1140-1615
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute /ID# 1140-0349
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center /ID# 1140-0020
🇺🇸Boston, Massachusetts, United States
Fred Hutchinson Cancer Research Center /ID# 1140-0404
🇺🇸Seattle, Washington, United States
Hopital de Brabois /ID# 1140-0775
🇫🇷Vandoeuvre-lès-nancy, Meurthe-et-Moselle, France
CHU Sainte-Justine /ID# 1140-1143
🇨🇦Montreal, Quebec, Canada
Duplicate_University of Tsukuba Hospital /ID# 1140-1445
🇯🇵Tsukuba-shi, Ibaraki, Japan
Kumamoto Medical Center /ID# 1140-1431
🇯🇵Kumamoto, Japan
Osaka Women's and Children's Hospital /ID# 1140-1440
🇯🇵Izumi-Shi, Osaka, Japan
Hokkaido University Hospital /ID# 1140-1436
🇯🇵Sapporo, Japan
Hospital Clinic /ID# 1140-0533
🇪🇸Barcelona, Spain
Stony Brook University Medical Center /ID# 1140-0719
🇺🇸New York, New York, United States
Columbia University Medical Center, MS-CHONY /ID# 1140-1124
🇺🇸New York, New York, United States
Weill Cornell Physicians - Hematologic Malignancies & Bone Marrow Transplant /ID# 1140-0019
🇺🇸New York, New York, United States
LPCH Stanford /ID# 1140-1128
🇺🇸Palo Alto, California, United States
Emory University/Winship Cancer Institute /ID# 1140-1179
🇺🇸Atlanta, Georgia, United States
Children's National Medical Center /ID# 1140-1122
🇺🇸Washington, District of Columbia, United States
University of Chicago /ID# 1140-0126
🇺🇸Chicago, Illinois, United States
University of Kentucky /ID# 1140-1140
🇺🇸Lexington, Kentucky, United States
University of Maryland /ID# 1140-0205
🇺🇸Baltimore, Maryland, United States
Hackensack University Medical Center/ John Theurer Cancer Center /ID# 1140-0343
🇺🇸Hackensack, New Jersey, United States
New York Presbyterian Hospital/Weill Cornell Med College /ID# 1140-0200
🇺🇸New York, New York, United States
University of Rochester Cancer Center /ID# 1140-0127
🇺🇸Rochester, New York, United States
West Virginia University /ID# 1140-1090
🇺🇸Morgantown, West Virginia, United States
Westmead Hospital /ID# 1140-0848
🇦🇺Westmead, New South Wales, Australia
The Kinghorn Cancer Centre /ID# 1140-1165
🇦🇺Darlinghurst, New South Wales, Australia
Royal Children's Hospital/ID# 1140-1154
🇦🇺Parkville, Victoria, Australia
Royal Melbourne Hospital (RMH) /ID# 1140-0633
🇦🇺Parkville, Victoria, Australia
Krankenhaus der Elisabethinen Linz /ID# 1140-0849
🇦🇹Linz, Austria
Fiona Stanley Hospital /ID# 1140-0880
🇦🇺Perth, Western Australia, Australia
Univ. Klinik for Innere Medizin, Klinische Abteilung for Hematologie, Graz /ID# 1140-0373
🇦🇹Graz, Austria
The Ottawa Hospital Regional Cancer Center /ID# 1140-0159
🇨🇦Ottawa, Ontario, Canada
Chinese PLA General Hospital /ID# 1140-1198
🇨🇳Beijing, China
The First Affiliated Hospital of Soochow University /ID# 1140-1208
🇨🇳Suzhou, Jiangsu, China
Nanfang Hospital /ID# 1140-1379
🇨🇳Guangzhou Shi, China
CHU de GRENOBLE Alpes /ID# 1140-1058
🇫🇷Grenoble, France
CHU Amiens Groupe hospitalier Sud /ID# 1140-1205
🇫🇷Amiens, France
Centre Hospitalier Regional Universitaire de Lille /ID# 1140-0750
🇫🇷Lille, France
Groupe Hospitalier Pitie-Salpetriere /ID# 1140-0918
🇫🇷Paris, France
Robert Bosch Hospital /ID# 1140-1160
🇩🇪Stuttgart, Baden-Wuerttemberg, Germany
CHU de Nantes /ID# 1140-0520
🇫🇷Nantes, France
Universitatsklinikum Munster /ID# 1140-1195
🇩🇪Munster, Niedersachsen, Germany
Universitaetsklinikum Dresden /ID# 1140-1367
🇩🇪Dresden, Germany
Hannover Medical School /ID# 1140-1141
🇩🇪Hannover, Germany
University Hospital of Regensburg /ID# 1140-1446
🇩🇪Regensburg, Germany
A.O. Univ. Ospedali Riuniti /ID# 1140-0932
🇮🇹Ancona, Marche, Italy
Ospedale San Raffaele IRCCS /ID# 1140-0523
🇮🇹Milan, Italy
University of Torino /ID# 1140-1268
🇮🇹Torino, Italy
Anjou Kousei Hospital /ID# 1140-1435
🇯🇵Anjo, Aichi, Japan
ASST Papa Giovanni XXIII /ID# 1140-1231
🇮🇹Bergamo, Italy
Kobe City Medical Center General Hospital /ID# 1140-1438
🇯🇵Kobe-shi, Hyogo, Japan
Duplicate_Kurashiki Central Hospital /ID# 1140-1442
🇯🇵Kurishiki-shi, Okayama, Japan
Tokai University Hospital /ID# 1140-1444
🇯🇵Isehara-shi, Kanagawa, Japan
Osaka City University Hospital /ID# 1140-1157
🇯🇵Osaka-shi, Osaka, Japan
National Center for Child Health and Development /ID# 1140-1443
🇯🇵Setagaya-ku, Tokyo, Japan
Cath Univ Seoul St Mary's Hosp /ID# 1140-0928
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center /ID# 1140-0963
🇰🇷Seoul, Korea, Republic of
National University Cancer Institute - National University Health System /ID# 1140-1155
🇸🇬Singapore, Singapore
Hospital Universitario Virgen del Rocio /ID# 1140-0863
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia /ID# 1140-1145
🇪🇸Valencia, Spain
Princess Margaret Cancer Centre /ID# 1140-0043
🇨🇦Toronto, Ontario, Canada
Samsung Medical Center /ID# 1140-0925
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Rutgers Cancer Institute of NJ /ID# 1140-0803
🇺🇸New Brunswick, New Jersey, United States
St. Laszlo Hospital /ID# 1140-1164
🇭🇺Budapest, Hungary
Hopital Saint-Louis - Institut Hematologie Centre Hayem CHU /ID# 1140-0735
🇫🇷Paris, Ile-de-France, France
Royal Brisbane and Women's Hospital /ID# 1140-0190
🇦🇺Herston, Queensland, Australia
Hospital Santa Creu i Sant Pau /ID# 1140-0535
🇪🇸Barcelona, Spain
Ucsf /Id# 1140-0003
🇺🇸San Francisco, California, United States
University of Louisville Hospital /ID# 1140-1131
🇺🇸Louisville, Kentucky, United States
University of Minnesota /ID# 1140-0807
🇺🇸Minneapolis, Minnesota, United States
UCHSC Anschultz Cancer Pavilion /ID# 1140-0068
🇺🇸Aurora, Colorado, United States
Florida Hospital Cancer Institute/Adventist Health System/Sunbelt, Inc /ID# 1140-1121
🇺🇸Orlando, Florida, United States
Barbara Ann Karmanos Cancer In /ID# 1140-0130
🇺🇸Detroit, Michigan, United States
Mayo Clinic, Rochester, MN /ID# 1140-0240
🇺🇸Rochester, Minnesota, United States
Vanderbilt University Medical Center Vanderbilt Ingram Cancer Center /ID# 1140-0024
🇺🇸Nashville, Tennessee, United States
Methodist San Antonio /ID# 1140-1118
🇺🇸San Antonio, Texas, United States
UHC Zagreb /ID# 1140-1169
🇭🇷Zagreb, Croatia
Dup_Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 1140-1439
🇯🇵Bunkyo-ku, Tokyo, Japan
University of British Columbia (UBC) - Vancouver General Hospital (VGH) /ID# 1140-1166
🇨🇦Vancouver, British Columbia, Canada
Montefiore Medical Center - Moses Campus /ID# 1140-0120
🇺🇸Bronx, New York, United States
University of North Carolina - Lineberger Comprehensive Cancer Center /ID# 1140-1133
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina, MUSC /ID# 1140-0738
🇺🇸Charleston, South Carolina, United States