A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT04923893
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to compare the efficacy of Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by a single administration of ciltacabtagene autoleucel (cilta-cel) versus VRd induction followed by Lenalidomide and Dexamethasone (Rd) maintenance in newly diagnosed multiple myeloma participants for whom ASCT is not planned as initial therapy in terms of Progression Free Survival (PFS).
- Detailed Description
Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. JNJ-68284528 (ciltacabtagene autoleucel \[cilta-cel\]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B lymphocytes and malignant plasma cells. The primary hypothesis of this study is that in participants with newly diagnosed MM, treatment with VRd induction followed by a single administration of cilta-cel will significantly improve progression free survival compared to Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by Rd maintenance. The study will screen participants with newly diagnosed MM who are not planned to receive autologous stem cell transplant (ASCT) as initial therapy. This study will be conducted in 4 phases: Screening (up to 28 days), Pre-randomization Treatment, Treatment, and Follow-up. Assessments like patient-reported outcome(s) (PROs), electrocardiogram (ECG), vital signs and pharmacokinetics will be performed during the study. Safety evaluations will include review of adverse events, laboratory test results, vital sign measurements, physical examination findings, assessment of cardiac function, Immune-Effector Cell-Associated Encephalopathy (ICE) and handwriting assessments (only for Arm B) and Eastern Cooperative Oncology Group (ECOG) performance status. Safety data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 12 years 5 months.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 650
- Documented diagnosis of multiple myeloma (MM) according to International Myeloma Working Group (IMWG) diagnostic criteria
- Measurable disease at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=)1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours; or Light chain MM in whom only measurable disease is by serum free light chain (FLC) levels: Serum immunoglobin (Ig) free light chain >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa/lambda FLC ratio
- Eastern Cooperative Oncology Group Performance Status grade of 0 or 1
- Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age; or Ineligible due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or Deferral of high-dose chemotherapy with ASCT as initial treatment
- A woman of childbearing potential (WOCBP) must have 2 negative highly sensitive serum or urine pregnancy tests (beta-human chorionic gonadotropin) prior to starting Bortezomib, Lenalidomide and Dexamethasone (VRd) and must agree to further testing during the study.
- Clinical laboratory values meeting the following criteria during the screening phase: hemoglobin greater than or equal to (>=) 8.0 g/dL (>=5 millimoles per liter [mmol/L]), recombinant human erythropoietin use is permitted; platelets >=75 *10^9/L; absolute lymphocyte count >=0.3 *10^9/L; absolute neutrophil count (ANC) >=1.0 ×10^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to (<=) 3.0 * upper limit of normal (ULN); estimated glomerular filtration rate >=40 milliliter per minute/1.73 meter square (mL/min/1.73 m^2) based upon modified diet in renal disease formula (MDRD-4) calculation or a 24-hour urine collection; total bilirubin <=2.0 * ULN; except in participants with congenital hyperbilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=2.0 * ULN is required)
- Frailty index of >=2 according to Myeloma Geriatric Assessment score
- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5
- Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
- Stroke or seizure within 6 months of signing Informed Consent Form (ICF)
- Seropositive for human immunodeficiency virus (HIV)
- Vaccinated with live, attenuated vaccine within 4 weeks prior to first dose of VRd
- Participant must not require continuous supplemental oxygen
- Hepatitis B infection
- Hepatitis C infection
- Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
- Any therapy that is targeted to B-cell maturation antigen (BCMA)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Cilta-cel Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). Arm A: VRd+Rd (Standard Therapy) Bortezomib Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m\^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity. Arm A: VRd+Rd (Standard Therapy) Dexamethasone Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m\^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity. Arm A: VRd+Rd (Standard Therapy) Lenalidomide Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m\^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity. Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Bortezomib Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Lenalidomide Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Fludarabine Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Dexamethasone Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Cyclophosphamide Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg).
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Up to 4 years and 5 months Progression-free survival is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD), as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to 12 years and 5 months Overall survival is measured from the date of randomization to the date of the participant's death.
Overall MRD Negative CR Up to 12 years and 5 months Overall MRD negative is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy.
Sustained Minimal Residual Disease (MRD) Negative CR Up to 12 years and 5 months Sustained MRD negative complete response (CR) as determined by next generation sequencing (NGS) with sensitivity of 10\^-5, and defined by MRD negative CR plus at least 12 months durability of the MRD negative CR status.
MRD Negative CR at 9 Months 9 months MRD negative CR rate at 9 months is defined as the percentage of participants who achieve MRD negative CR status at 9±3 months after the randomization date.
Complete Response or Better Up to 12 years and 5 months CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to the IMWG criteria.
Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score Baseline up to 12 years and 5 months The EORTC QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
Time to Subsequent Anti-myeloma Therapy Up to 12 years and 5 months Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy.
Progression Free Survival on Next-line Therapy (PFS2) Up to 12 years and 5 months PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.
Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs Up to 12 years and 5 months Number of participants with AEs, abnormalities in laboratory parameters (complete blood count \[CBC\] with differential, coagulation, chimeric antigen receptor T cell \[CAR-T\] chemistry, full metabolic panel etc.), 12-lead ECG, physical examination, and vital signs will be reported.
Arm B: Systemic Cytokine Concentrations Up to Day 112 Serum or plasma proteomic profiling of cytokines (such as interleukin \[IL\] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment.
Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers Up to 12 years and 5 months CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry, cytometry by time of flight (CyTOF), single cell RNA sequencing (scRNAseq) or similar technologies and be correlated with response.
Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA) Up to 1 year Levels of soluble BCMA will be reported.
Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence Up to 12 years and 5 months Levels of cilta-cel expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Arm B: Number of Participants with Anti-cilta-cel Antibodies Up to 12 years and 5 months Number of participants with anti-cilta-cel antibodies will be reported.
Arm B: Number of Participants with Presence of Replication Competent Lentivirus Up to 12 years and 5 months Number of participants with presence of replication competent lentivirus will be reported.
Time to Worsening of Symptoms, Functioning and Overall Well-being Up to 12 year and 5 months Time to worsening is measured as the interval from the date of randomization to the start date of worsening in MySIm-Q symptom, impact, or total scores.
Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score Baseline up to 12 years and 5 months The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact.
Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score Baseline up to 12 years and 5 months The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems, where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems, plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score Baseline up to 12 years and 5 months The PGIS uses 2 items to assess the participant's perception of the severity of their disease symptoms and impact using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).
Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items Up to 161 days The National Cancer Institute's PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference that ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.
Trial Locations
- Locations (135)
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University Of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
New York Presbyterian-Weill Cornell Medical College
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Hospital Aleman
🇦🇷Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Buenos Aires, Argentina
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, Argentina
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Australia
Austin Health
🇦🇺Heidelberg, Australia
Royal Brisbane and Womens Hospital
🇦🇺Herston, Australia
Alfred Health
🇦🇺Melbourne, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Australia
Calvary Mater Newcastle Hospital
🇦🇺Waratah, Australia
Western Sydney Local Health District
🇦🇺Westmead, Australia
Medizinische Universität Graz, LKH-Univ.Klinikum Graz, Klinische Abteilung für Hämatologie
🇦🇹Graz, Austria
Krankenhaus der Elisabethinen Linz
🇦🇹Linz, Austria
LKH - Universitätsklinikum der PMU Salzburg
🇦🇹Salzburg, Austria
Medical University of Vienna Universitatsklinik fur Innere Medizin I
🇦🇹Vienna, Austria
Universitair Ziekenhuis - Antwerpen
🇧🇪Antwerp, Belgium
AZ St.-Jan Brugge-Oostende AV
🇧🇪Brugge, Belgium
UZ Gent
🇧🇪Gent, Belgium
Fundacao Antonio Prudente A C Camargo Cancer Center
🇧🇷Sao Paulo, Brazil
UZ Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
🇧🇪Liege, Belgium
Hospital Sao Rafael
🇧🇷Salvador, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
🇧🇷Sao Paulo, Brazil
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Princess Margaret Cancer Centre University Health Network
🇨🇦Toronto, Ontario, Canada
Hopital Maisonneuve Rosemont
🇨🇦Montreal, Quebec, Canada
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni Nemocnice Ostrava
🇨🇿Ostrava - Poruba, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Aarhus University Hospital
🇩🇰Aarhus C, Denmark
CHU Poitiers - Hopital la Miletrie
🇫🇷Poitiers, France
Rigshospitalet
🇩🇰Copenhagen, Denmark
Odense Universitetshospital
🇩🇰Odense C, Denmark
Helsinki University Hospital
🇫🇮Helsinki, Finland
Oulu University Hospital
🇫🇮Oulu, Finland
Institut Universitaire du cancer de Toulouse-Oncopole
🇫🇷Toulouse cedex 9, France
Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin
🇩🇪Berlin, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Germany
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
Turku University Hospital
🇫🇮Turku, Finland
Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
🇫🇷Lille Cedex, France
C.H.U. Hotel Dieu - France
🇫🇷Nantes, France
Hopital Saint Louis
🇫🇷Paris cedex 10, France
Universitaetsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinikum Großhadern der Ludwig-Maximilians-Universität
🇩🇪München, Germany
Universitaetsklinikum Regensburg
🇩🇪Regensburg, Germany
Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
🇩🇪Tubingen, Germany
Universitatsklinikum Wurzburg
🇩🇪Wuerzburg, Germany
Japanese Red Cross Medical Center
🇯🇵Shibuya, Japan
Alexandra General Hospital of Athens
🇬🇷Athens, Greece
Attikon University General Hospital of Attica
🇬🇷Athens, Greece
G.Papanikolaou
🇬🇷Thessaloniki, Greece
Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
St James Hospital
🇮🇪Dublin, Ireland
Hadassah University Hospita Ein Kerem
🇮🇱Jerusalem, Israel
Sheba Medical Center Tel Hashomer
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Juntendo University Hospital
🇯🇵Bunkyo Ku, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Hyogo Medical University Hospital
🇯🇵Hyôgo, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Japan
Tohoku University Hospital
🇯🇵Sendai, Japan
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
UMC Radboud
🇳🇱Nijmegen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznan, Poland
Oslo universitetssykehus HF, Rikshospitalet
🇳🇴Oslo, Norway
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach
🇵🇱Gliwice, Poland
Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
🇵🇱Lublin, Poland
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Instituto Portugues de Oncologia
🇵🇹Porto, Portugal
Hosp. de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Instituto Catalan Deoncologia Hospital Duran I Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. Virgen de La Arrixaca
🇪🇸Murcia, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Hosp. Univ. I Politecni La Fe
🇪🇸Valencia, Spain
Sahlgrenska University Hospital
🇸🇪Goteborg, Sweden
Universitetssjukhuset
🇸🇪Linköping, Sweden
Skane University Hospital
🇸🇪Lund, Sweden
Universitatsspital Basel
🇨🇭Basel, Switzerland
Kantonsspital St Gallen
🇨🇭St. Gallen, Switzerland
University Hospitals Birmingham NHS Trust,
🇬🇧Birmingham, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
The Royal Marsden NHS Trust Sutton
🇬🇧Surrey, United Kingdom
Arthur J E Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Universitatsmedizin der Johannes Gutenberg Universitat Mainz
🇩🇪Mainz, Germany
Inselspital Universitatsspital Bern
🇨🇭Bern, Switzerland
UCSF
🇺🇸San Francisco, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
University of Miami Health System
🇺🇸Miami, Florida, United States
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Medical College Of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
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