Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
- Conditions
- Non-Hodgkins LymphomaHematologic MalignanciesWaldenstroms MacroglobulinaemiaChronic Lymphocytic Leukaemia
- Interventions
- Registration Number
- NCT04728893
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).
- Detailed Description
This study will be performed in 2 parts: Dose Escalation and Confirmation (Part 1) and Cohort Expansion (Part 2). Following determination of the recommended phase 2 dose (RP2D) in Part 1, the study plans to proceed with Part 2 using 8 disease-specific expansion cohorts (Cohorts A to H).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 490
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
- Has a life expectancy of at least 3 months, based on the investigator assessment
- Has the ability to swallow and retain oral medication
- Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
- Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- Has adequate organ function
- Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
- Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention
- Participants with HIV are eligible if they meet all of the following: the CD4 count is >350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART
Part 1 and Part 2 (Cohorts A to C and J)
-
Has a confirmed diagnosis of CLL/SLL with
- At least 2 lines of prior therapy (Part 1 only)
- Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
- Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
- Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
- Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i
- Has active disease for CLL/SLL clearly documented to initiate therapy
- Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)
Part 2 (Cohorts D to G)
-
Has a confirmed diagnosis of and meets the following prior therapy requirements:
- Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
- Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
- Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)
- Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
-
Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan
-
Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening
Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
- Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
- Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
- Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
- Has active HBV/HCV infection (Part 1 and Part 2)
- Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen <10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
- Has active central nervous system (CNS) disease
- Has an active infection requiring systemic therapy
- Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- Has any clinically significant gastrointestinal abnormalities that might alter absorption
- History of severe bleeding disorders
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nemtabrutinib Nemtabrutinib Participants receive nemtabrutinib orally once daily (QD) until progressive disease (PD) or discontinuation.
- Primary Outcome Measures
Name Time Method Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR) Up to ~61 months ORR per iwCLL 2018 criteria is defined as the percentage of participants achieving a complete response (CR), complete response with incomplete bone marrow recovery (CRi), nodular partial response (nPR), or partial response (PR). CR is defined as meeting the following criteria: no lymph nodes \>1.5 cm, spleen size \<13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10\^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10\^9/L or ≥50% increase from screening, hemoglobin \>11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Part 2: ORR per Lugano criteria 2014 as assessed by ICR Up to ~61 months ORR per Lugano criteria 2014 is defined as the percentage of participants achieving a CR or PR. CR defined as EITHER CR by imaging (computed tomography \[CT\]): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR complete metabolic response (CMR): score of 1, 2 or 3 on the 5-point scale assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions (ranging from 1=no uptake above background to 5=uptake markedly higher than liver) AND bone marrow (BM) normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the sum of the product of diameters \[SPD\] of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with score of 4 or 5 on the FDG 5-point scale (with no new lesions) and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Part 2: ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR Up to ~71 months ORR per IWWM criteria 2014 is defined as the percentage of participants achieving a CR, very good partial response (VGPR), or PR. CR is defined as all lymph nodes are normal in size (none ≥15 mm), liver and spleen normal in size, serum immunoglobulin M (IgM) values in the normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with a second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal), and ≥90% decrease from baseline in serum IgM, or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in serum IgM, and ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal).
Part 1: Number of participants discontinuing study treatment due to AEs Up to ~42 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to an AE will be reported for Part 1.
Part 1: Number of participants experiencing adverse events (AEs) Up to ~71 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 1.
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs) Up to ~56 days (Cycles 1-2, cycle = 28 days) DLTs will be defined as toxicities observed during the first 2 cycles (8 weeks) of Part 1 and include: Grade ≥3 nonhematologic toxicity (except Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension which will not be considered a DLT unless lasting ≥72 hours despite optimal supportive care); Grade 4 hematologic toxicity lasting \>7 days (except Grade 3 lymphocytosis, Grade 4 platelet count decreased of any duration, or Grade 3 platelet count decreased if associated with bleeding); any Grade 3 or Grade 4 nonhematologic laboratory abnormality if values result in drug-induced liver injury, or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for \>1 week (with exceptions); missing \>25% of nemtabrutinib doses as a result of drug-related adverse events (AEs) during the first 2 cycles (8 weeks); Grade 5 toxicity.
- Secondary Outcome Measures
Name Time Method Part 1: Area Under the Curve (AUC) of Nemtabrutinib At designated time points (up to ~57 days) Blood samples will be obtained at designated time points during Part 1 for the assessment of nemtabrutinib AUC (Day 1 of Cycles 1 and 2: Pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2, 4, and 6 hours post-dose \[up to \~57 days\]). Each cycle is 28 days.
Part 2: Number of participants discontinuing study treatment due to AEs Up to ~42 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to an AE will be reported for Part 2.
Part 2: Cmin of Nemtabrutinib At designated time points (up to ~57 days) Blood samples will be obtained at designated time points during Part 2 for the assessment of nemtabrutinib Cmin (Day 1 of Cycles 1, 2, and 3: Pre-dose, 2, 4, 6, hours post-dose \[up to \~57 days\]). Each cycle is 28 days.
Part 2: Cmax of Nemtabrutinib At designated time points (up to ~57 days) Blood samples will be obtained at designated time points during Part 2 for the assessment of nemtabrutinib Cmax (Day 1 of Cycles 1, 2, and 3: Pre-dose, 2, 4, 6, hours post-dose \[up to \~57 days\]). Each cycle is 28 days.
Part 1: Minimum Concentration (Cmin) of Nemtabrutinib At designated time points (up to ~57 days) Blood samples will be obtained at designated time points during Part 1 for the assessment of nemtabrutinib Cmin (Day 1 of Cycles 1 and 2: Pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2, 4, and 6 hours post-dose \[up to \~57 days\]). Each cycle is 28 days.
Part 1: ORR per iwCLL criteria 2018 as assessed by ICR Up to ~71 months ORR per iwCLL 2018 criteria is defined as the percentage of participants achieving a CR, CRi, nPR, or PR. CR is defined as meeting the following criteria: no lymph nodes \>1.5 cm, spleen size \<13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10\^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10\^9/L or ≥50% increase from screening, hemoglobin \>11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR Up to ~71 months For participants with CR, CRi, nPR, or PR per iwCLL 2018 criteria, DOR is defined as the time from the first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes \>1.5 cm, spleen size \<13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10\^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10\^9/L or ≥50% increase from screening, hemoglobin \>11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Part 1: Maximum Concentration (Cmax) of Nemtabrutinib At designated time points (up to ~57 days) Blood samples will be obtained at designated time points during Part 1 for the assessment of nemtabrutinib Cmax (Day 1 of Cycles 1 and 2: Pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2, 4, and 6 hours post-dose \[up to \~57 days\]). Each cycle is 28 days.
Part 2: Number of participants experiencing AEs Up to ~61 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 2.
Part 2: DOR per iwCLL criteria 2018 as assessed by ICR Up to ~61 months For participants with CR, CRi, nPR, or PR per iwCLL 2018 criteria, DOR is defined as the time from the first documented evidence of objective response until disease progression or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes \>1.5 cm, spleen size \<13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10\^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10\^9/L or ≥50% increase from screening, hemoglobin \>11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Part 2: DOR per Lugano criteria 2014 as assessed by ICR Up to ~61 months For participants with CR or PR per Lugano criteria 2014, DOR is defined as the time from the first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as EITHER CR by imaging (CT): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR CMR: score of 1, 2 or 3 on the 5-point scale assessing FDG metabolic activity in lymphomatous lesions (ranging from 1=no uptake above background to 5=uptake markedly higher than liver and/or new lesions) AND BM normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR PMR with score of 4 or 5 on the FDG 5-point scale (with no new lesions) and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Part 2: DOR per IWWM criteria 2014 as assessed by ICR Up to ~61 months For participants with CR, VGPR, or PR per IWWM criteria 2014, DOR defined as the time from first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as all lymph nodes normal in size (none ≥15 mm), liver and spleen normal in size, serum IgM values in normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal), and ≥90% decrease from baseline in serum IgM, or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in serum IgM, and ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal).
Part 2: AUC of Nemtabrutinib At designated time points (up to ~57 days) Blood samples will be obtained at designated time points during Part 2 for the assessment of nemtabrutinib AUC (Day 1 of Cycles 1, 2, and 3: Pre-dose, 2, 4, 6, hours post-dose \[up to \~57 days\]). Each cycle is 28 days.
Trial Locations
- Locations (121)
Rambam Medical Center ( Site 1301)
🇮🇱Haifa, Israel
Highlands Oncology Group ( Site 2728)
🇺🇸Springdale, Arkansas, United States
University of California San Diego Moores Cancer Center ( Site 2717)
🇺🇸La Jolla, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site 2724)
🇺🇸Torrance, California, United States
Colorado Blood Cancer Institute ( Site 2726)
🇺🇸Denver, Colorado, United States
The University of Louisville, James Graham Brown Cancer Center ( Site 2729)
🇺🇸Louisville, Kentucky, United States
Mayo Clinic - Rochester ( Site 2706)
🇺🇸Rochester, Minnesota, United States
Astera Cancer Care ( Site 2732)
🇺🇸East Brunswick, New Jersey, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704)
🇺🇸Hackensack, New Jersey, United States
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2708)
🇺🇸Fargo, North Dakota, United States
UT Southwestern-Harold C. Simmons Cancer Center ( Site 2730)
🇺🇸Dallas, Texas, United States
Medical Oncology Associates (Summit Cancer Centers) ( Site 2710)
🇺🇸Spokane, Washington, United States
Hospital Aleman ( Site 0102)
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103)
🇦🇷Buenos Aires, Caba, Argentina
Fundacion Estudios Clinicos ( Site 0112)
🇦🇷Rosario, Santa Fe, Argentina
FUNDALEU ( Site 0104)
🇦🇷Caba, Argentina
Hospital Privado Universitario de Córdoba ( Site 0107)
🇦🇷Cordoba, Argentina
Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 0110)
🇦🇷Mendoza, Argentina
Nepean Hospital-Nepean Cancer Care Centre ( Site 0204)
🇦🇺Sydney, New South Wales, Australia
Box Hill Hospital ( Site 0203)
🇦🇺Box Hill, Victoria, Australia
Sir Charles Gairdner Hospital ( Site 0200)
🇦🇺Nedlands, Western Australia, Australia
Hospital das Clinicas FMUSP-Pesquisa Clínica Hematologia ( Site 0303)
🇧🇷São Paulo, Sao Paulo, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0300)
🇧🇷Rio de Janeiro, Brazil
BP - A Beneficencia Portuguesa de São Paulo ( Site 0302)
🇧🇷Sao Paulo, Brazil
Hospital Paulistano - Amil Clinical Research ( Site 0311)
🇧🇷Sao Paulo, Brazil
Arthur J.E. Child Comprehensive Cancer Centre ( Site 0401)
🇨🇦Calgary, Alberta, Canada
The Ottawa Hospital ( Site 0404)
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0406)
🇨🇦Toronto, Ontario, Canada
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0403)
🇨🇦Montreal, Quebec, Canada
Jewish General Hospital ( Site 0400)
🇨🇦Montreal, Quebec, Canada
Anhui Provincial Hospital ( Site 2808)
🇨🇳Hefei, Anhui, China
Peking University Third Hospital-Hematology ( Site 2827)
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of Chongqing Medical University ( Site 2825)
🇨🇳Chongqing, Chongqing, China
Sun Yat-sen University Cancer Center-Internal Medicine ( Site 2824)
🇨🇳Guangzhou, Guangdong, China
Guangxi Medical University - Liuzhou Renmin Hospital ( Site 2817)
🇨🇳Liuzhou, Guangxi, China
Guangxi Medical University Affiliated Tumor Hospital ( Site 2814)
🇨🇳Nanning, Guangxi, China
Soroka Medical Center ( Site 1307)
🇮🇱Beer-Sheva, Israel
Henan Cancer Hospital-hematology department ( Site 2802)
🇨🇳Zhengzhou, Henan, China
Wuhan Union Hospital ( Site 2816)
🇨🇳Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University ( Site 2820)
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital ( Site 2822)
🇨🇳Changsha, Hunan, China
Jiangsu Province Hospital ( Site 2823)
🇨🇳Nanjing, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical College ( Site 2818)
🇨🇳Xuzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University ( Site 2815)
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University-Hematology ( Site 2803)
🇨🇳Changchun, Jilin, China
Fudan University Shanghai Cancer Center ( Site 2801)
🇨🇳Shanghai, Shanghai, China
Huashan Hospital, Fudan University ( Site 2821)
🇨🇳Shanghai, Shanghai, China
West China Hospital Sichuan University ( Site 2810)
🇨🇳Cheng Du, Sichuan, China
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Unio ( Site 2800)
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University ( Site 2826)
🇨🇳Hangzhou, Zhejiang, China
Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0600)
🇨🇿Brno, Brno-mesto, Czechia
Fakultni nemocnice Hradec Kralove ( Site 0601)
🇨🇿Hradec Kralove, Czechia
Aarhus University Hospital ( Site 0702)
🇩🇰Aarhus N, Midtjylland, Denmark
Aalborg Universitetshospital ( Site 0703)
🇩🇰Aalborg, Nordjylland, Denmark
Sjaellands Universitetshospital Roskilde ( Site 0701)
🇩🇰Roskilde, Sjaelland, Denmark
Odense University Hospital ( Site 0705)
🇩🇰Odense C, Syddanmark, Denmark
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 0810)
🇫🇷Nice, Alpes-Maritimes, France
Institut Paoli-Calmettes ( Site 0803)
🇫🇷Marseille, Bouches-du-Rhone, France
Centre Hospitalier Lyon-Sud ( Site 0804)
🇫🇷Pierre Benite, Rhone-Alpes, France
Centre Hospitalier de Versailles ( Site 0809)
🇫🇷Le Chesnay, Yvelines, France
Hopital Saint Louis ( Site 0805)
🇫🇷Paris, France
Universitaetsklinikum Ulm. ( Site 0906)
🇩🇪Ulm, Baden-Wurttemberg, Germany
Universitaetsklinikum Koeln ( Site 0901)
🇩🇪Koeln, Nordrhein-Westfalen, Germany
St. Marien-Krankenhaus Siegen ( Site 0914)
🇩🇪Siegen, Nordrhein-Westfalen, Germany
Universitaetsklinikum Carl Gustav Carus ( Site 0902)
🇩🇪Dresden, Sachsen, Germany
Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar ( Site 1202)
🇭🇺Pecs, Baranya, Hungary
Debreceni Egyetem Klinikai Kozpont ( Site 1201)
🇭🇺Debrecen, Hajdu-Bihar, Hungary
Szabolcs Szatmár Bereg Vármegyei Oktatókórház ( Site 1206)
🇭🇺Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary
Orszagos Onkologiai Intezet ( Site 1200)
🇭🇺Budapest, Hungary
Beaumont Hospital ( Site 2900)
🇮🇪Dublin, Ireland
University Hospital Limerick ( Site 2903)
🇮🇪Limerick, Ireland
Ha Emek Medical Center ( Site 1305)
🇮🇱Afula, Israel
Hadassah Ein Karem Jerusalem ( Site 1300)
🇮🇱Jerusalem, Israel
Chaim Sheba Medical Center ( Site 1302)
🇮🇱Ramat Gan, Israel
Kaplan Medical Center ( Site 1304)
🇮🇱Rehovot, Israel
Sourasky Medical Center ( Site 1303)
🇮🇱Tel Aviv, Israel
Istituto Tumori Giovanni Paolo II ( Site 1409)
🇮🇹Bari, Italy
A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 1400)
🇮🇹Bologna, Italy
ASST Spedali Civili di Brescia ( Site 1408)
🇮🇹Brescia, Italy
IRCCS Ospedale San Raffaele ( Site 1402)
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1403)
🇮🇹Napoli, Italy
Fondazione IRCCS Policlinico San Matteo ( Site 1407)
🇮🇹Pavia, Italy
IRCCS - Arcispedale Santa Maria Nuova ( Site 1405)
🇮🇹Reggio Emilia, Italy
Policlinico Umberto I ( Site 1404)
🇮🇹Roma, Italy
Severance Hospital Yonsei University Health System ( Site 2201)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 2200)
🇰🇷Seoul, Korea, Republic of
Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site 1606)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Pratia MCM Krakow ( Site 1601)
🇵🇱Krakow, Malopolskie, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site 1608)
🇵🇱Warszawa, Mazowieckie, Poland
Szpital Wojewódzki w Opolu-Hematology Department ( Site 1607)
🇵🇱Opole, Opolskie, Poland
Szpitale Pomorskie Sp. z o.o. ( Site 1600)
🇵🇱Gdynia, Pomorskie, Poland
Ovidius Clinical Hospital ( Site 1804)
🇷🇴Ovidiu, Constanta, Romania
Institutul Regional de Oncologie Iasi ( Site 1801)
🇷🇴Iasi, Romania
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 2000)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Spitalul Clinic Colțea ( Site 1805)
🇷🇴București, Bucuresti, Romania
Centrul de Diagnostic si Tratament Oncologic Brasov ( Site 1802)
🇷🇴Brasov, Romania
Hospital Universitari Vall d'Hebron ( Site 2001)
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre ( Site 2003)
🇪🇸Madrid, Spain
Inselspital Bern ( Site 2303)
🇨🇭Bern, Berne, Switzerland
Hospital Universitario de Salamanca ( Site 2002)
🇪🇸Salamanca, Castilla Y Leon, Spain
CHUAC-Complejo Hospitalario Universitario A Coruña ( Site 2005)
🇪🇸A Coruña, La Coruna, Spain
Hospital General Universitario de Alicante ( Site 2007)
🇪🇸Alicante, Spain
Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 2302)
🇨🇭Bellinzona, Ticino, Switzerland
Mega Medipol-Hematology ( Site 2406)
🇹🇷Stanbul, Istanbul, Turkey
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi ( Site 2400)
🇹🇷Ankara, Turkey
VKV Amerikan Hastanesi ( Site 2403)
🇹🇷Istanbul, Turkey
Sisli Florence Nightingale Hastanesi ( Site 2407)
🇹🇷Istanbul, Turkey
Dokuz Eylül Üniversitesi-Hematology ( Site 2402)
🇹🇷Izmir, Turkey
MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 2509)
🇺🇦Cherkassy, Cherkaska Oblast, Ukraine
Communal non-profit enterprise "Regional clinical hospital o-Hematology Department ( Site 2510)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Instit. of Blood Transfusion Medicine of the National Academy ( Site 2506)
🇺🇦Lviv, Lvivska Oblast, Ukraine
National Cancer Institute ( Site 2507)
🇺🇦Kyiv, Ukraine
Kyiv City Clinical Hospital 9 ( Site 2502)
🇺🇦Kyiv, Ukraine
Bristol Haematology and Oncology Centre ( Site 2610)
🇬🇧Bristol, Bristol, City Of, United Kingdom
Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 2601)
🇬🇧Nottingham, England, United Kingdom
GenesisCare - Windsor ( Site 2608)
🇬🇧Windsor, England, United Kingdom
Sarah Cannon Research Institute UK ( Site 2612)
🇬🇧London, London, City Of, United Kingdom
GenesisCare - Oxford ( Site 2607)
🇬🇧Oxford, Oxfordshire, United Kingdom
GenesisCare - Cambridge ( Site 2611)
🇬🇧Newmarket, Suffolk, United Kingdom
The Royal Marsden NHS Foundation Trust. ( Site 2606)
🇬🇧Sutton, Surrey, United Kingdom
The Christie NHS Foundation Trust ( Site 2602)
🇬🇧Manchester, United Kingdom