A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

Phase 1

Recruiting

• Conditions: Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B Cell Lymphoma; B-cell Malignancy; Small Lymphocytic Lymphoma; Follicular Lymphoma; Waldenström Macroglobulinemia; Non-Hodgkin Lymphoma; Mantle Cell Lymphoma
• Interventions: Drug: BGB-16673

• Registration Number: NCT05006716
• Lead Sponsor: BeiGene

Brief Summary

Study consists of two main parts to explore BGB-16673 recommended dosing, a Phase 1 monotherapy dose finding comprised of monotherapy dose escalation and monotherapy safety expansion of selected doses, and a Phase 2 (expansion cohorts)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-09
• Study First Submitted QC: 2021-08-09
• Study First Posted: 2021-08-16
• Study Start: 2021-09-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-18
• Primary Completion: 2025-03-31
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 621

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Prior malignancy (other than the disease under study) within the past 2 years, except in situ malignancies that have been curatively resected, localized breast cancer treated with curative intent with no evidence of breast active disease for more than 3 years and receiving adjuvant hormonal therapy, localized Gleason score ≤ 6 prostate cancer undergoing observation or treatment with androgen depravation, or any other cancer treated with curative intent, not on adjuvant treatment, and in the opinion of the investigator is unlikely to recur.
2. Requires ongoing systemic treatment for any other malignancy
3. Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment.
4. Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by B-cell malignancy, regardless of whether participants had received treatment for central nervous system disease
5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, germinal center B-cell (GCB), DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary cutaneous DLBCL - leg type, DLBCL associated with chronic inflammation, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma - NOS, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma, or history of or currently suspected transformation of an indolent lymphoma to an aggressive histology (except for participants with Richter Transformation to DLBCL are eligible for Part 1a, 1c, or Phase 2 and participants with history of follicular lymphoma transforming to non-GCB DLBCL who are eligible for Part 1a, 1c, or Phase 2).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 1a (Monotherapy Dose Escalation)	BGB-16673	Dose escalation in specific subtypes of non-Hodgkin lymphoma (NHL), including relapsed or refractory (R/R) marginal zone lymphoma (MZL), relapsed or refractory (R/R) follicular lymphoma (FL) Grades 1, 2, and 3a, relapsed or refractory (R/R) mantle cell lymphoma (MCL), relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), relapsed or refractory (R/R) Richter's transformation (RT), and relapsed or refractory (R/R) Waldenström macroglobulinemia (WM), to evaluate the safety and tolerability of BGB-16673.
Part 1b (Monotherapy Safety Expansion)	BGB-16673	Participants with R/R MZL, MCL, CLL/SLL, and WM will be enrolled at selected doses to help determine the recommended dose(s) for expansion (RDFE(s)) for BGB-16673.
Part 1c (Additional Monotherapy Safety Expansion)	BGB-16673	Additional safety data will be collected from participants with R/R MZL, WM, RT, DLBCL, or FL to confirm the RDFE(s) of BGB-16673 for those with non-CLL/SLL/MCL histologies.
Part 1d (Additional Monotherapy Safety Expansion in R/R CLL/SLL)	BGB-16673	Participants with R/R CLL/SLL will be enrolled at selected RDFE(s) to generate additional safety and efficacy data for BGB-16673.
Part 1e (Japan-only Cohort)	BGB-16673	Japanese participants with R/R MZL, FL, MCL, CLL/SLL, and WM will be enrolled at selected RDFE(s) to assess the safety and tolerability of BGB-16673.
Part 1f (Additional Monotherapy Safety Expansion in BTKi Naive B-Cell Malignancies)	BGB-16673	Participants with CLL/SLL, MCL, WM, MZL, or Richter's transformation to DLBCL who have not received a prior BTKi (either covalent or noncovalent) will be enrolled at selected dose levels.
Phase 2 (Monotherapy Expansion)	BGB-16673	Cohorts of participants with R/R CLL/SLL, R/R MCL, R/R WM, R/R MZL, R/R FL, R/R RT, and R/R DLBCL will be enrolled to recieve the RDFE(s) identified in Phase 1 to further evaluate the safety and efficacy of BGB-16673.

Primary Outcome Measures

Name	Time	Method
Phase 1: Number of Participants with Adverse Events (AEs)	From the first dose of BGB-16673 until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (Up to 47 weeks)	Number of participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) including results from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicities (DLTs); as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-16673	Approximately 28 days	MTD is defined as the highest evaluated dose with an estimated toxicity rate closest to the target, while MAD is the highest dose given if MTD is not reached.
Phase 1: Recommended dose(s) for Expansion (RDFE) of BGB-16673	Approximately 28 days	RDFE of BGB-16673 alone will be determined based upon the MTD or MAD.
Phase 2: Overall response rate (ORR)	approximately 3 years	Defined as the percentage of participants achieving a best overall response of partial response (PR) or better, assessed by the Independent Review Committee for participants with R/R CLL/SLL and R/R MCL and by the investigator for other cohorts (R/R WM, R/R FL, R/R non-GCB DLBCL, R/R Ritchter's transformation to DLBCL), evaluated using the Lugano criteria for NHL and SLL, iwCLL criteria for CLL, and IWWM-6 criteria for WM.

Secondary Outcome Measures

Name	Time	Method
Single dose and steady-state maximum observed plasma concentration (Cmax) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state minimum observed plasma concentration (Cmin) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state time to reach Cmax (tmax) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state time to reach half of Cmax (T1/2) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state area under the plasma concentration-time curve (AUC) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state apparent volume of distribution (Vz/F) of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Single dose and steady-state accumulation ratios of BGB-16673	Week 1 Day 1 pre-dose; 2, 4, 6, 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose; and 2, 4, 6, 8 post-dose; Week 9 Day 1 pre-dose.
Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy	Week 1 Day 1 pre-dose; 8, 24, 48, and 72 hours post-dose; Week 5 Day 1 pre-dose and 8 hours post-dose; Week 9 Day 1 pre-dose.
Phase 1: Overall response rate (ORR)	approximately 3 years	Defined as the percentage of participants whose best overall response is better than stable disease, as assessed by the investigator and evaluated according to the following criteria: the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for R/R CLL, the International Workshop on Waldenström's Macroglobulinemia (IWWM-6) criteria for R/R WM, and the Lugano criteria for R/R NHL.
Phase 1: Number of R/R WM Participants with major response rate (MRR)	approximately 3 years	MRR is defined as the percentage of participants whose best overall response (BOR) is partial response (PR) or better (PR, very good partial response (VGPR), or complete response (CR)) as assessed by the investigator and evaluated per the IWWM-6 criteria.
Phase 2: Response rate of minor response or better	approximately 3 years	Defined as the percentage of participants who achieve at least a minor response (MR) or a more favorable outcome, as assessed by investigators for cohort 3 (R/R WM)
Phase 2: Duration of Response (DOR)	approximately 3 years	DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is documented or death, whichever comes first as assessed by the investigator and the IRC.
Phase 2: Time to Response (TTR)	approximately 3 years	TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by IRC and the investigator
Phase 1: Number of Participants with AEs in part 1e (Japan-only cohort )	From the first dose of BGB-16673 in Part 1e until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (approximately 3 years)	Number of Japanese participants in Part 1e with TEAEs and SAEs, including results from laboratory assessments, ECGs, and physical examinations, that meet protocol-defined DLTs, graded according to the NCI-CTCAE v5.0.
Phase 2: Recommended Phase 2 Dose (RP2D)	approximately 3 years	Defined as the dose of a drug recommended for use in Phase 2 clinical trials, the Recommended Phase 2 Dose (RP2D) is determined by the sponsor based on the Safety Monitoring Committee's recommendations, taking into account the overall clinical safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data.
Phase 2: Number of Participants with AEs	From the first dose of BGB-16673 in Phase 2 until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (approximately 3 years)	Number of participants with TEAEs and SAEs, including results from laboratory assessments, ECGs, and physical examinations, that meet protocol-defined DLTs, graded according to the NCI-CTCAE v5.0.
Phase 2: Complete Response Rate (CRR)	approximately 3 years	CRR for participants in Cohort 2 (R/R blastoid or nonblastoid variant R/R MCL) is defined as the percentage of participants who achieve a complete response (CR), as determined by both the Independent Review Committee (IRC) and investigators.
Phase 2: Progression- Free Survival (PFS)	approximately 3 years	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by IRC and the investigator
Phase 2: Overall Survival (OS)	approximately 3 years	OS is defined as the time from first study drug administration to the date of death due to any cause
Phase 2: Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionaire	Baseline and day 1 of Weeks 5, 13, 25, and 37	Mean change from baseline in the 'physical well-being' and 'functional well-being' subscales of the FACT-Leu for Cohort 1 participants (R/R CLL/SLL). FACT-Leu is a 44-item PRO questionnaire with five subscales used to measure health-related quality of life (HRQoL) in leukemia patients.
Phase 2: National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18)	Baseline and day 1 of Weeks 5, 13, 25, and 37	Mean change from baseline in the NFlymSI-18 subscales of disease-related symptoms (DRSP) and 'treatment side effects' for Cohort 2 participants (R/R MCL). The NFlymSI-18 is an 18-item patient-reported outcome (PRO) tool specifically designed to assess symptoms and treatment impacts in patients with non-Hodgkin lymphoma.

Trial Locations

Locations (118)

Western Regional Medical Center, Llc; 🇺🇸 Goodyear, Arizona, United States

Honor Health Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Mount Sinai Comprehensive Cancer Center; 🇺🇸 Miami Beach, Florida, United States

Augusta University; 🇺🇸 Augusta, Georgia, United States

Southeastern Regional Medical Center; 🇺🇸 Newnan, Georgia, United States

Midwestern Regional Medical Center; 🇺🇸 Zion, Illinois, United States

American Oncology Partners of Maryland Pa; 🇺🇸 Bethesda, Maryland, United States

Nebraska Cancer Specialists; 🇺🇸 Grand Island, Nebraska, United States

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Summit Medical Group; 🇺🇸 Florham Park, New Jersey, United States

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Peninsula Private Hospital; 🇦🇺 Frankston, Victoria, Australia

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Hospital Sirio Libanes Brasilia; 🇧🇷 Brasilia, Brazil

Instituto de Pesquisa Em Saude Da Universidade de Caxias Do Sul; 🇧🇷 Caxias do Sul, Brazil

Hospital Ernesto Dornelles; 🇧🇷 Porto Alegre, Brazil

Centro Gaucho Integrado de Oncologia Hospital Mae de Deus; 🇧🇷 Porto Alegre, Brazil

Real E Benemerita Associacao Portuguesa de Sao Paulo; 🇧🇷 Sao Paulo, Brazil

Instituto Dor de Pesquisa E Ensino Sao Paulo; 🇧🇷 Sao Paulo, Brazil

Hospital Alemao Oswaldo Cruz; 🇧🇷 Sao Paulo, Brazil

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein; 🇧🇷 Sao Paulo, Brazil

Hospital Santa Rita de Cassia Afecc; 🇧🇷 Vitoria, Brazil

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

British Columbia Cancer Agency the Vancouver Centre; 🇨🇦 Vancouver, British Columbia, Canada

Arthur Je Child Comprehensive Cancer Centre; 🇨🇦 Calgary, Canada

Chu de Quebec Universite Laval, Hopital de Lenfant Jesus, Centre Integre de Cancerologie (Cic); 🇨🇦 Quebec, Canada

Hopital Claude Huriez Chu Lille; 🇫🇷 Lille, France

Centre Henri Becquerel; 🇫🇷 Rouen Cedex, France

Uniklinik Koln (Aor); 🇩🇪 Koln, Germany

Universitares Krebszentrum Leipzig; 🇩🇪 Leipzig, Germany

Klinikum Grosshadern Ludwig Maximilians Universitat Munchen; 🇩🇪 Munich, Germany

Aichi Cancer Center Hospital Clinical Oncology; 🇯🇵 Nagoya, Aichi, Japan

Chiba Cancer Center; 🇯🇵 Chibashi, Chiba, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan

Cancer Institute Hospital of Jfcr; 🇯🇵 Kotoku, Tokyo, Japan

Yokohama Municipal Citizens Hospital; 🇯🇵 Yokohamashi, Japan

Inje University Busan Paik Hospital; 🇰🇷 Busan, Busan Gwang'yeogsi, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Busan Gwang'yeogsi, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

The Catholic University of Korea, Seoul St Marys Hospital; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Hospital de La Santa Creu I Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario Vall Dhebron; 🇪🇸 Barcelona, Spain

Md Anderson Cancer Center Madrid Spain; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Uppsala Akademiska Sjukhus; 🇸🇪 Uppsala, Sweden

Dr Abdurrahman Yurtaslan Research and Training Hospital; 🇹🇷 Ankara, Turkey

Ankara University; 🇹🇷 Ankara, Turkey

Dokuz Eylul University; 🇹🇷 Izmir, Turkey

Sakarya Training and Research Hospital; 🇹🇷 Sakarya, Turkey

Ondokuz Mayis University; 🇹🇷 Samsun, Turkey

Edinburgh Cancer Centre; 🇬🇧 Edinburgh, United Kingdom

Churchill Hospital Oxford University Hospital Nhs Trust; 🇬🇧 Headington, United Kingdom

Freeman Hospital; 🇬🇧 NewCastle Upon Tyne, United Kingdom

Nottingham University Hospitals Nhs Trust; 🇬🇧 Nottingham, United Kingdom

Derriford Hospital; 🇬🇧 Plymouth, United Kingdom

University of Alabama At Birmingham Hospital; 🇺🇸 Birmingham, Alabama, United States

Mayo Clinic Phoenix; 🇺🇸 Phoenix, Arizona, United States

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

University of California San Diego (Ucsd) Moores Cancer Center; 🇺🇸 La Jolla, California, United States

UCLA Santa Monica Cancer Care; 🇺🇸 Santa Monica, California, United States

Stanford Medicine; 🇺🇸 Stanford, California, United States

Uchealth North; 🇺🇸 Fort Collins, Colorado, United States

Mayo Clinic Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Tampa General Hospital Cancer Institute; 🇺🇸 Tampa, Florida, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

Norton Cancer Institute Pavilion; 🇺🇸 Louisville, Kentucky, United States

Mary Bird Perkins Cancer Center; 🇺🇸 Baton Rouge, Louisiana, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

Weill Cornell Medical College Newyork Presbyterian Hospital; 🇺🇸 New York, New York, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center Mskcc; 🇺🇸 New York, New York, United States

Tennessee Oncology, Pllc Nashville; 🇺🇸 Nashville, Tennessee, United States

Md Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Virginia Commonwealth University Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Concord Repatriation General Hospital; 🇦🇺 Concord, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

St Vincents Hospital Melbourne; 🇦🇺 Fitzroy, Victoria, Australia

Peter Maccallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

Perth Blood Institute; 🇦🇺 West Perth, Western Australia, Australia

Hospital Erasto Gaertner; 🇧🇷 Curitiba, Brazil

Hospital Nove de Julho Dasa; 🇧🇷 Sao Paulo, Brazil

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Centre de Lutte Contre Le Cancer Institut Bergonie; 🇫🇷 Bordeaux, France

Hopital Estaing; 🇫🇷 Clermont Ferrand, France

Chu Henri Mondor; 🇫🇷 Creteil, France

Centre Leon Berard; 🇫🇷 Lyon Cedex, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Chu Montpellier Hopital Saint Eloi; 🇫🇷 Montpellier Cedex, France

Hopital de La Pitie Salpetriere; 🇫🇷 Paris, France

Arensia Exploratory Medicine Llc; 🇬🇪 Tbilisi, Georgia

Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden; 🇩🇪 Dresden, Germany

Universitaetsklinikum Schleswig Holstein Campus Luebeck; 🇩🇪 Luebeck, Germany

Klinikum Johannes Gutenberg Universitaet Mainz; 🇩🇪 Mainz, Germany

Universitaetsklinikum Ulm, Innere Medizin Iii; 🇩🇪 Ulm, Germany

Policlinico Sorsola Malpighi, Aou Di Bologna; 🇮🇹 Bologna, Italy

Ospedale San Raffaele; 🇮🇹 Milano, Italy

Istituto Europeo Di Oncologia; 🇮🇹 Milano, Italy

Niguarda Cancer Center Division of Hematology; 🇮🇹 Milano, Italy

Fondazione Policlinico Universitario Agostino Gemelli; 🇮🇹 Roma, Italy

Centroricerche Cliniche Di Verona Srl; 🇮🇹 Verona, Italy

Severance Hospital Yonsei University Health System; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

The Institute of Oncology, Arensia Exploratory Medicine; 🇲🇩 Chisinau, Moldova, Republic of

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro Majadahonda; 🇪🇸 Majadahonda, Spain

Sahlgrenska University Hospital Hematology; 🇸🇪 Goteborg, Sweden

Karolinska Universitetssjukhuset Solna; 🇸🇪 Stockholm, Sweden

Erciyes University; 🇹🇷 Kayseri, Turkey

St Jamess University Hospital; 🇬🇧 Leeds, United Kingdom