A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

Phase 3

Active, not recruiting

• Conditions: Acute Myeloid Leukemia (AML)
• Interventions: Drug: Azacitidine; Drug: Placebo; Drug: Venetoclax

• Registration Number: NCT02993523
• Lead Sponsor: AbbVie

Brief Summary

Acute Myeloid Leukaemia (AML) is an aggressive and rare cancer of myeloid cells (a white blood cell responsible for fighting infections). Successful treatment of AML is dependent on what subtype of AML the participant has, and the age of the participant when diagnosed.

Venetoclax is an experimental drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. This study is designed to see if adding venetoclax to azacitidine works better than azacitidine on its own.

This is a Phase 3, randomized, double-blind (treatment is unknown to participants and doctors), placebo controlled study in patients with AML who are \>= 18 or more years old and have not been treated before. Participants who take part in this study should not be suitable for standard induction therapy (usual starting treatment). AbbVie is funding this study which will take place at approximately 180 hospitals globally and enroll approximately 400 participants.

In this study, 2/3 of participants will receive venetoclax every day with azacitidine and the remaining 1/3 will receive placebo (dummy) tablets with azacitidine.

Participants will continue to have study visits and receive treatment for as long as they are having a clinical benefit. The effect of the treatment on AML will be checked by taking blood, bone marrow, scans, measuring side effects and by completing health questionnaires. Blood and bone marrow tests will be completed to see why some people respond better than others. Additional blood tests will be completed for genetic factors and to see how long the drug remains in the body.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-13
• Study First Submitted QC: 2016-12-13
• Study First Posted: 2016-12-15
• Study Start: 2017-02-02
• Primary Completion: 2021-12-01
• Results First Submitted: 2022-11-28
• Results First Submitted QC: 2023-01-11
• Results First Posted: 2023-01-27
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-17
• Last Update Posted: 2024-06-27
• Study Completion: 2026-01-23

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 443

Inclusion Criteria

• Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.

• Participant must be >= 18 years of age.

• Participant must have a projected life expectancy of at least 12 weeks.

• Participant must be considered ineligible for induction therapy defined by the following:

  a. >= 75 years of age; or b. >= 18 to 74 years of age with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; ii. Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; iii. Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; iv. Creatinine clearance >= 30 mL/min to < 45 ml/min; v. Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); vi. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the AbbVie Therapeutic Medical Director during screening and before study enrollment.

• Participant must have an ECOG Performance status:

  1. 0 to 2 for Participants >= 75 years of age or
  2. 0 to 3 for Participants >= 18 to 74 years of age.

• Participant must have adequate renal function as demonstrated by a creatinine >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.

• Participant must have adequate liver function as demonstrated by:

  1. aspartate aminotransferase (AST) <= 3.0 x ULN*
  2. alanine aminotransferase (ALT) <= 3.0 x ULN*
  3. bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ involvement

  i. Participants who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

• Female participants must be either postmenopausal defined as:

  1. Age > 55 years with no menses for 12 or more months without an alternative medical cause.
  2. Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an follicle stimulating hormone (FSH) level >40 international units per liter (IU/L); or
  3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); or
  4. Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.

• Male participants who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.

• Female participants of childbearing potential must have negative results for pregnancy test performed:

  1. At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
  2. Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.

• Participant must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria

• Participant has received treatment with the following:

  1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
  2. Chimeric Antigen Receptor (CAR)-T cell therapy.
  3. Experimental therapies for MDS or Acute Myeloid Leukemia (AML).
  4. Current participation in another research or observational study.

• Participant has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.

• Participant has the following:

  a. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 for Acute Myeloid Leukemia.

• Participant has acute promyelocytic leukemia

• Participant has known active central nervous system (CNS) involvement with AML.

• Participant has known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax) HIV testing will be performed at Screening, only if required per local guidelines or institutional standards.

• Participant is known to be positive for hepatitis B or C infection [HCV Ab indicative of a previous or current infection; and/or positive HBs Ag or detected sensitivity on hepatitis B virus (HBV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test for HBc Ab and/or HBs Ab positivity] with the exception of those with an undetectable viral load within 3 months screening. Hepatitis B or C testing is not required.

• Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment; additional details as described in the protocol.

• Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.

• Participant has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.

• Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.

• Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.

• Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).

• Participant has a history of other malignancies within 2 years prior to study entry, with the exception of:

  1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  3. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.

• Participant has a white blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis are permitted to meet this criterion.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2	Azacitidine	Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax-matching placebo, orally, every day (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2	Placebo	Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax-matching placebo, orally, every day (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Azacitidine	Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2	Venetoclax	Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Venetoclax	Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2	Azacitidine	Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the study start up to death or alive or lost to follow-up (up to approximately 4.8 years; data cut off date: 1 December 2021)	OS is defined as the number of days from the date of randomization to the date of death. Log rank test was used to compare the OS distribution between two treatment arms. Cox regression was used to report the hazard ratio.
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi)	From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)	CR and CRi was calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count \>10\^3/ microliter (mcL), platelets \>10\^5/mcL, red cell transfusion independence, and bone marrow with \<5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤10\^3/mcL or platelets ≤10\^5/mcL. Percentages are rounded off to whole number at the nearest decimal.

Secondary Outcome Measures

Name	Time	Method
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)	Measured up to 2 years after the last participant is randomized	A response of CRh is defined as Bone marrow with \<5% blasts, peripheral blood neutrophil count \>0.5\*10\^3/mcL and peripheral blood platelet count \>0.5\*10\^5/mcL.
Post Baseline Transfusion Independence Rate	Measured up to 2 years after the last participant is randomized	Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.
Complete Remission (CR) Rate	Measured up to 2 years after the last participant is randomized	The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.
Event-free Survival (EFS)	Measured up to 2 years after the last participant is randomized	EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.
Global Health Status/Quality of Life (GHS/QoL)	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit	Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).
Percentage of Participants Achieving Composite Complete Remission (CR or CRi)	Up to 6 months after the first 225 participants are randomized	This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count \> 10\^3/mcL, platelets \> 10\^5/mcL, red cell transfusion independence, and bone marrow with \< 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of \<= 10\^3/mcL or platelets \<= 10\^5/mcL.
Fatigue/Quality of Life (QoL)	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit	Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a global fatigue score

Trial Locations

Locations (172)

Emory Midtown Infectious Disease Clinic /ID# 162534; 🇺🇸 Atlanta, Georgia, United States

Northwestern University Feinberg School of Medicine /ID# 201133; 🇺🇸 Chicago, Illinois, United States

University of Chicago Medicine /ID# 154108; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University /ID# 154104; 🇺🇸 Baltimore, Maryland, United States

University Of Vermont Medical /ID# 157196; 🇺🇸 Burlington, Vermont, United States

Massachusetts General Hospital /ID# 200752; 🇺🇸 Boston, Massachusetts, United States

Kyiv Regional Onco Dispensary /ID# 153514; 🇺🇦 Kyiv, Ukraine

Royal Adelaide Hospital /ID# 154271; 🇦🇺 Adelaide, South Australia, Australia

St Vincent's Hospital Melbourne /ID# 155094; 🇦🇺 Melbourne, Victoria, Australia

Royal Perth Hospital /ID# 154274; 🇦🇺 Perth, Western Australia, Australia

University of California, Davis Comprehensive Cancer Center /ID# 162725; 🇺🇸 Sacramento, California, United States

Norton Cancer Institute /ID# 154992; 🇺🇸 Louisville, Kentucky, United States

Fort Wayne Medical Oncology /ID# 157190; 🇺🇸 Fort Wayne, Indiana, United States

Juravinski Cancer Centre /ID# 153650; 🇨🇦 Hamilton, Ontario, Canada

Sepctrum Health Medical Center /ID# 159522; 🇺🇸 Grand Rapids, Michigan, United States

Alfred Health /ID# 154275; 🇦🇺 Melbourne, Victoria, Australia

Beth Israel Deaconess Medical Center /ID# 201155; 🇺🇸 Boston, Massachusetts, United States

Instituto do Câncer do Estado de São Paulo - ICESP /ID# 153095; 🇧🇷 São Paulo, Sao Paulo, Brazil

Princess Margaret Cancer Centre /ID# 153651; 🇨🇦 Toronto, Ontario, Canada

Duplicate_Landeskrankenhaus Salzburg /ID# 169719; 🇦🇹 Salzburg, Austria

UCL Saint-Luc /ID# 153391; 🇧🇪 Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium

Ottawa Hospital Research Institute /ID# 153541; 🇨🇦 Ottawa, Ontario, Canada

Sir Charles Gairdner Hospital /ID# 163924; 🇦🇺 Nedlands, Western Australia, Australia

Instituto de Ensino e Pesquisa São Lucas /ID# 157778; 🇧🇷 São Paulo, Sao Paulo, Brazil

CHU Bordeaux - Hopital Haut Leveque /ID# 153789; 🇫🇷 Pessac, Gironde, France

Chu Angers /Id# 153792; 🇫🇷 Angers, France

Gunmaken Saiseikai Maebashi Hospital /ID# 168316; 🇯🇵 Maebashi-shi, Gunma, Japan

Columbia Univ Medical Center /ID# 154101; 🇺🇸 New York, New York, United States

Hitachi General Hospital /ID# 201109; 🇯🇵 Hitachi-shi, Ibaraki, Japan

Assaf Harofeh Medical Center /ID# 158063; 🇮🇱 Be'er Ya'aqov, Israel

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 153099; 🇧🇷 Ribeirão Preto, Sao Paulo, Brazil

Fondazione PTV Policlinico Tor Vergata /ID# 152881; 🇮🇹 Rome, Roma, Italy

Princess Alexandra Hospital /ID# 154272; 🇦🇺 Woolloongabba, Queensland, Australia

The Royal Melbourne Hospital /ID# 155095; 🇦🇺 Parkville, Victoria, Australia

Ordensklinikum Linz GmbH Elisabethinen /ID# 154885; 🇦🇹 Linz, Oberoesterreich, Austria

Hanusch Krankenhaus /ID# 155676; 🇦🇹 Wien, Austria

UZ Gent /ID# 153392; 🇧🇪 Gent, Oost-Vlaanderen, Belgium

UZ Brussel /ID# 153393; 🇧🇪 Jette, Bruxelles-Capitale, Belgium

Tom Baker Cancer Centre /ID# 159645; 🇨🇦 Calgary, Alberta, Canada

Fakultni nemocnice Hradec Kralove /ID# 154021; 🇨🇿 Hradec Kralove, Czechia

Tampere University Hospital /ID# 154963; 🇫🇮 Tampere, Pirkanmaa, Finland

Klinicki bolnicki centar Zagreb /ID# 153383; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Azienda Ospedaliero-Universitaria Sant'Andrea /ID# 152876; 🇮🇹 Rome, Italy

University of Fukui Hospital /ID# 167432; 🇯🇵 Yoshida-gun, Fukui, Japan

Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 158990; 🇭🇺 Budapest, Hungary

IUCT Oncopole /ID# 153788; 🇫🇷 Toulouse Cedex 9, France

National Hospital Organization Kyushu Cancer Center /ID# 201111; 🇯🇵 Fukuoka-shi, Fukuoka, Japan

Universitaetsklinikum Muenster /ID# 153059; 🇩🇪 Muenster, Nordrhein-Westfalen, Germany

Universitaetsklinikum Frankfurt /ID# 153060; 🇩🇪 Frankfurt am Main, Hessen, Germany

Debreceni Egyetem Klinikai Kozpont /ID# 153814; 🇭🇺 Debrecen, Hajdu-Bihar, Hungary

Turku University Hospital /ID# 154964; 🇫🇮 Turku, Finland

AP-HP - Hopital Saint-Louis /ID# 153787; 🇫🇷 Paris, France

Clinical Hospital Dubrava /ID# 153515; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Tel Aviv Sourasky Medical Center /ID# 154175; 🇮🇱 Tel Aviv-Yafo, Tel-Aviv, Israel

Duplicate_Semmelweis Egyetem /ID# 153815; 🇭🇺 Budapest, Hungary

Hadassah /ID# 154172; 🇮🇱 Jerusalem, Israel

Duplicate_Klinicki bolnicki centar Osijek /ID# 153623; 🇭🇷 Osijek, Osjecko-baranjska Zupanija, Croatia

Semmelweis Egyetem /ID# 153816; 🇭🇺 Budapest, Hungary

Fakultni nemocnice Ostrava /ID# 154017; 🇨🇿 Ostrava, Czechia

Fakultni nemocnice Plzen /ID# 154018; 🇨🇿 Plzen, Czechia

Fakultni Nemocnice Brno /ID# 154019; 🇨🇿 Brno, Czechia

Universitaetsklinikum Halle (Saale) /ID# 153058; 🇩🇪 Halle (Saale), Germany

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont /ID# 153812; 🇭🇺 Szeged, Csongrad, Hungary

Drammen Sykehus /ID# 154280; 🇳🇴 Drammen, Buskerud, Norway

Hospital Santa Creu i Sant Pau /ID# 153193; 🇪🇸 Barcelona, Spain

Medizinische Hochschule Hannover /ID# 153055; 🇩🇪 Hannover, Germany

The Chaim Sheba Medical Center /ID# 154173; 🇮🇱 Ramat Gan, Tel-Aviv, Israel

Rambam Health Care Campus /ID# 154174; 🇮🇱 Haifa, Israel

The Jikei University Daisan Hospital /ID# 168745; 🇯🇵 Komae-shi, Tokyo, Japan

IPO Porto FG, EPE /ID# 154138; 🇵🇹 Porto, Portugal

Saitama Medical University International Medical Center /ID# 167814; 🇯🇵 Hidaka-shi, Saitama, Japan

Yamagata University Hospital /ID# 167634; 🇯🇵 Yamagata-shi, Yamagata, Japan

Samsung Medical Center /ID# 153674; 🇰🇷 Seoul, Korea, Republic of

SP ZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 153385; 🇵🇱 Chorzow, Slaskie, Poland

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 171220; 🇮🇹 Ancona, Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 152883; 🇮🇹 Bologna, Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152882; 🇮🇹 Milan, Italy

Aichi Cancer Center Hospital /ID# 200824; 🇯🇵 Nagoya-shi, Aichi, Japan

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 168639; 🇯🇵 Bunkyo-ku, Tokyo, Japan

Sykehuset Ostfold Kalnes /ID# 157755; 🇳🇴 Gralum, Norway

Presidio Ospedaliero Vito Fazzi /ID# 170837; 🇮🇹 Lecce, Puglia, Italy

Duplicate_Kindai University Hospital /ID# 167662; 🇯🇵 Osaka-sayama-shi, Osaka, Japan

NTT Medical Center Tokyo /ID# 167975; 🇯🇵 Shinagawa-ku, Tokyo, Japan

Samara State Medical University /ID# 157462; 🇷🇺 Samara, Russian Federation

Kyushu University Hospital /ID# 169095; 🇯🇵 Fukuoka-shi, Fukuoka, Japan

Moscow State budget healthcare /ID# 155738; 🇷🇺 Moscow, Moskva, Russian Federation

Juntendo University Hospital /ID# 168309; 🇯🇵 Bunkyo-ku, Tokyo, Japan

Dup_VO Hematologi /ID# 153174; 🇸🇪 Lund, Sweden

Tohoku University Hospital /ID# 169259; 🇯🇵 Sendai-shi, Miyagi, Japan

Okayama University Hospital /ID# 204124; 🇯🇵 Okayama-shi, Okayama, Japan

Hospital Universitario Virgen de la Victoria /ID# 153257; 🇪🇸 Malaga, Spain

Seoul National University Hospital /ID# 153675; 🇰🇷 Seoul, Korea, Republic of

Hospital Universitario de la Princesa /ID# 153256; 🇪🇸 Madrid, Spain

University of Pretoria /ID# 153682; 🇿🇦 Pretoria, Gauteng, South Africa

Albert Alberts Stem Cell Transplant Centre /ID# 153684; 🇿🇦 Pretoria, Gauteng, South Africa

Hospital Universitario de Navarra /ID# 153254; 🇪🇸 Pamplona, Navarra, Spain

National Taiwan University Hospital /ID# 153900; 🇨🇳 Taipei City, Taiwan

Duplicate_Regional Oncology Dispensary /ID# 153264; 🇷🇺 Penza, Penzenskaya Oblast, Russian Federation

Hospital Clinic de Barcelona /ID# 153255; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Maranon /ID# 153260; 🇪🇸 Madrid, Spain

Akademiska Sjukhuset /ID# 153034; 🇸🇪 Uppsala, Uppsala Lan, Sweden

Karolinska University Hospital /ID# 170003; 🇸🇪 Stockholm, Sweden

Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 153902; 🇨🇳 Kaohsiung, Taiwan

Hospital de Clinicas de Porto Alegre /ID# 157779; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

St. Paul's Hospital /ID# 159644; 🇨🇦 Vancouver, British Columbia, Canada

Universitaetsklinikum St. Poelten /ID# 167436; 🇦🇹 Sankt Poelten, Niederoesterreich, Austria

Haukeland University Hospital /ID# 154281; 🇳🇴 Bergen, Hordaland, Norway

China Medical University Hospital /ID# 153904; 🇨🇳 Taichung City, Taiwan

Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 154888; 🇦🇹 Linz, Oberoesterreich, Austria

Kyiv city clinical hospital #9 /ID# 153510; 🇺🇦 Kiev, Vinnytska Oblast, Ukraine

Akershus universitetssykehus /ID# 154279; 🇳🇴 Nordlenangen, Akershus, Norway

Duplicate_Hospital de Braga /ID# 154797; 🇵🇹 Braga, Portugal

Changhua Christian Hospital /ID# 153899; 🇨🇳 Changhua city, Changhua County, Taiwan

Aalborg University Hospital /ID# 154047; 🇩🇰 Aalborg, Nordjylland, Denmark

University of Utah /ID# 157192; 🇺🇸 Salt Lake City, Utah, United States

Fujian Medical University Union Hospital /ID# 167314; 🇨🇳 Fuzhou, Fujian, China

Nanfang Hospital of Southern Medical University /ID# 170148; 🇨🇳 Guangzhou, Guangdong, China

Henan Cancer Hospital /ID# 167320; 🇨🇳 Zhengzhou, Henan, China

The First Hospital of Jilin University /ID# 167490; 🇨🇳 Changchun, Jilin, China

Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 167315; 🇨🇳 Wuhan, Hubei, China

Jiangsu Province Hospital /ID# 167489; 🇨🇳 Nanjing, Jiangsu, China

West China Hospital, Sichuan University /ID# 167492; 🇨🇳 Chengdu, Sichuan, China

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 167487; 🇨🇳 Tianjin, Tianjin, China

Qilu Hospital of Shandong University /ID# 167485; 🇨🇳 Jinan, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 167318; 🇨🇳 Shanghai, Shanghai, China

Ospedale Policlinico San Martino /ID# 158104; 🇮🇹 Genova, Italy

Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli /ID# 152879; 🇮🇹 Napoli, Italy

Osaka Metropolitan University Hospital /ID# 169055; 🇯🇵 Osaka-shi, Osaka, Japan

Hospital Universitario y Politecnico La Fe /ID# 153259; 🇪🇸 Valencia, Spain

Hospital Universitario 12 de Octubre /ID# 153258; 🇪🇸 Madrid, Spain

Federal State Budgetary Ins NRC for Hematology of MoH of Russian Federation /ID# 155740; 🇷🇺 Moscow, Russian Federation

Ankara Universitesi Fakultesi /ID# 155200; 🇹🇷 Ankara, Turkey

City of Hope /ID# 154105; 🇺🇸 Duarte, California, United States

University of California, Los Angeles /ID# 154107; 🇺🇸 Los Angeles, California, United States

Cotton-O'Neil Clinical Res Ctr /ID# 155136; 🇺🇸 Topeka, Kansas, United States

EMMC Cancer Care /ID# 154991; 🇺🇸 Brewer, Maine, United States

University of Pittsburgh MC /ID# 154102; 🇺🇸 Pittsburgh, Pennsylvania, United States

Dana-Farber Cancer Institute /ID# 167009; 🇺🇸 Boston, Massachusetts, United States

Tennessee Oncology-Nashville Centennial /ID# 200854; 🇺🇸 Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center /ID# 154100; 🇺🇸 Houston, Texas, United States

Duke Cancer Center /ID# 154106; 🇺🇸 Durham, North Carolina, United States

Baylor Scott & White Medical Center- Temple /ID# 157191; 🇺🇸 Temple, Texas, United States

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 165077; 🇺🇸 New York, New York, United States

Medizinische Universitaet Graz /ID# 157882; 🇦🇹 Graz, Steiermark, Austria

AZ Sint-Jan Brugge /ID# 154041; 🇧🇪 Brugge, Belgium

The Second Hospital of Hebei Medical University /ID# 167316; 🇨🇳 Shijiazhuang, Hebei, China

Helsinki University Hospital /ID# 155223; 🇫🇮 Helsinki, Uusimaa, Finland

The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 167317; 🇨🇳 Hangzhou, Zhejiang, China

Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 153813; 🇭🇺 Kaposvár, Somogy, Hungary

Universitaetsklinikum Ulm /ID# 153054; 🇩🇪 Ulm, Baden-Wuerttemberg, Germany

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 169854; 🇭🇺 Nyíregyháza, Nyiregyhaza, Hungary

Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 153056; 🇩🇪 Hamburg, Germany

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 152875; 🇮🇹 Bergamo, Italy

National Hospital Organization Mito Medical Center /ID# 168219; 🇯🇵 Higashi, Ibaraki, Japan

Rabin Medical Center /ID# 154176; 🇮🇱 Petach Tikva, Israel

Duplicate_Kyoto Prefectural University of Medicine /ID# 167661; 🇯🇵 Kyoto-shi, Kyoto, Japan

Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 152877; 🇮🇹 Reggio Calabria, Italy

Nagasaki University Hospital /ID# 168632; 🇯🇵 Nagasaki-shi, Nagasaki, Japan

Duplicate_Konkuk University Medical Ctr /ID# 153973; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym im. Ludwika Rydygiera w /ID# 169846; 🇵🇱 Krakow, Malopolskie, Poland

VA Caribbean Healthcare System /ID# 160507; 🇵🇷 San Juan, Puerto Rico

Kuzbass Regional Clinical Hospital /ID# 157461; 🇷🇺 Kemerovo, Kemerovskaya Oblast, Russian Federation

Saratov State Medical University n.a. V.I. Razumovskiy /ID# 153267; 🇷🇺 Saratov, Saratovskaya Oblast, Russian Federation

Nizhny Novgorod Regional Clinical Hospital named N.A. Semashko /ID# 153268; 🇷🇺 Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation

State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 157460; 🇷🇺 Ryazan, Ryazanskaya Oblast, Russian Federation

Uddevalla sjukhus /ID# 156875; 🇸🇪 Uddevalla, Vastra Gotalands Lan, Sweden

Ondokuz Mayis Universitesi Tip /ID# 155201; 🇹🇷 Samsun, Turkey

Hacettepe University Faculty of Medicine /ID# 202073; 🇹🇷 Ankara, Turkey

Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 153511; 🇺🇦 Dnipro, Ukraine

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu /ID# 153389; 🇵🇱 Wroclaw, Dolnoslaskie, Poland

Poltava Reg Clin Hosp Sklifoso /ID# 153513; 🇺🇦 Poltava, Ukraine

Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167493; 🇨🇳 Wuhan, Hubei, China