Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT03871829
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to compare the efficacy (rate of very good partial response \[VGPR\] or better as best response as defined by the International Myeloma Working Group \[IMWG\] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.
- Detailed Description
For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 to 3 prior line(s) of treatment including a line containing daratumumab to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 88
- Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to daratumumab-containing therapy with response duration of at least 4 months
- Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or >60 days after cessation of treatment
- Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram per day [mg/day] for 4 days) would not be considered prior lines of therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
- Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
- Previous treatment with daratumumab within the last 3 months prior to randomization
- Discontinuation of daratumumab due to a daratumumab-related adverse event (AE)
- History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
- Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count <350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART >4 weeks plus having HIV viral load <400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Dara-SC in combination with Kd (DKd) Dexamethasone 40 mg Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm A: Carfilzomib+Dexamethasone (Kd) Dexamethasone 20 mg Participants will receive carfilzomib 20 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m\^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm A: Carfilzomib+Dexamethasone (Kd) Dexamethasone 40 mg Participants will receive carfilzomib 20 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m\^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm B: Dara-SC in combination with Kd (DKd) Carfilzomib 20 mg/m^2 Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm B: Dara-SC in combination with Kd (DKd) Dara-SC 1800 mg Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm B: Dara-SC in combination with Kd (DKd) Dexamethasone 20 mg Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm B: Dara-SC in combination with Kd (DKd) Carfilzomib 70 mg/m^2 Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm A: Carfilzomib+Dexamethasone (Kd) Carfilzomib 20 mg/m^2 Participants will receive carfilzomib 20 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m\^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days. Arm A: Carfilzomib+Dexamethasone (Kd) Carfilzomib 70 mg/m^2 Participants will receive carfilzomib 20 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m\^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response Up to 3 years and 4 months Percentage of participants achieving VGPR or better response were reported. VGPR or better rate was defined as the percentage of participants achieving VGPR, complete response (CR), or stringent complete response (sCR) in accordance with the International Myeloma Working Group (IMWG) criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (\>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (\<) 100 milligram (mg)/24 hours; for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow; for sCR: CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Negative Minimal Residual Disease (MRD) Up to 3 years and 7 months Percentage of participants with negative MRD were reported. MRD negativity rate, defined as the percentage of participants who had MRD negative status at 10\^-5 by bone marrow aspirate after the date of randomization and prior to PD or subsequent anti-myeloma therapy.
Time to Next Treatment Up to 3 years and 7 months Time to next treatment was defined as the time from randomization to the start of the next-line treatment.
Serum Concentrations of Daratumumab Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months) Serum concentrations of daratumumab were assessed. This outcome measure was planned to be analyzed for specified arm only.
Overall Response Rate (ORR) Up to 3 years and 7 months ORR was defined as the percentage of participants who achieved partial response (PR) or better responses based on the computerized algorithm, in accordance with the IMWG criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for PR: greater than or equal to (\>=)50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or less than (\<)200 mg/24 hours; If the serum and urine M-protein were not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria; If serum and urine M-protein were not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%; additionally, if present at baseline, \>=50% reduction in the size of soft tissue PCs was also required.
Percentage of Participants Achieving Complete Response (CR) or Better Up to 3 years and 7 months Percentage of participants achieving CR or better were reported. CR or better rate was defined as the percentage of participants achieving CR or sCR based on the computerized algorithm, according to IMWG response criteria. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow.
Progression Free Survival (PFS) Up to 3 years and 7 months PFS was defined as the duration from the date of randomization to either progressive disease (PD) or death, whichever comes first. IMWG criteria for PD: \>=25% from lowest response level in serum M-component (the absolute increase must be \>=0.5 gram per deciliter \[g/dL\]) and/or in urine M-component (the absolute increase must be \>=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of \>=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be \>10 mg/dL. BMPC%: the absolute % must be \>=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \>11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter \[mmol/L\]) that can be attributed solely to PC proliferative disorder.
Overall Survival (OS) Up to 3 years and 7 months OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies Up to end of study; up to 30.3 months The incidence of anti-rHuPH20 antibodies were summarized for all participants who received at least one dose of Dara-SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of Dara-SC). This outcome measure was planned to be analyzed for specified arm only.
Number of Participants With Anti-Daratumumab Antibodies Up to end of study; up to 30.3 months Number of participants who test positive for anti-daratumumab antibodies were reported. This outcome measure was planned to be analyzed for specified arm only.
Trial Locations
- Locations (108)
Zuyderland Medical Center
🇳🇱Sittard, Netherlands
University General Hospital of Rio
🇬🇷Patra, Greece
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Hosp. de Leon
🇪🇸Leon, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Aarhus University Hospital
🇩🇰Aarhus N, Denmark
Regionshospitalet i Holstebro
🇩🇰Holstebro, Denmark
Haematological Research unit HFE-X OUH.
🇩🇰Odense, Denmark
Institut Claudius Regaud
🇫🇷Toulouse, France
CHU Nancy Brabois
🇫🇷Vandoeuvre Les Nancy, France
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
American Institute of Research (AIR)
🇺🇸Whittier, California, United States
Oncology Institute of Hope and Innovation
🇺🇸Tucson, Arizona, United States
Fort Wayne Medical Oncology and Hematology, Inc.
🇺🇸Fort Wayne, Indiana, United States
Karmanos Cancer Institute - Wayne State University
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
Baylor Scott and White Health
🇺🇸Dallas, Texas, United States
Cleveland Clinic Main Campus
🇺🇸Cleveland, Ohio, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
Liga Paranaense de Combate ao Cancer
🇧🇷Curitiba, Brazil
Universidade Federal de Goias - Hospital das Clinicas da UFG
🇧🇷Goiania, Brazil
Universidade Estadual De Campinas
🇧🇷Campinas, Brazil
Liga Norte Riograndense Contra O Cancer
🇧🇷Natal, Brazil
Ministerio da Saude - Instituto Nacional do Cancer
🇧🇷Rio de Janeiro, Brazil
Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
🇧🇷Rio de Janeiro, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
CEHON
🇧🇷Salvador, Brazil
Hospital Sao Rafael
🇧🇷Salvador, Brazil
Instituto de Ensino e Pesquisa São Lucas
🇧🇷Sao Paulo, Brazil
Fundacao Antonio Prudente - A.C. Camargo Cancer Center
🇧🇷Sao Paulo, Brazil
Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
🇧🇷Sao Paulo, Brazil
Real e Benemérita Associação Portuguesa de Beneficência
🇧🇷São Paulo, Brazil
Clinica Sao Germano
🇧🇷São Paulo, Brazil
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Vejle Hospital
🇩🇰Vejle, Denmark
Centre Hospitalier Emile Muller
🇫🇷Mulhouse, France
Hopital Claude Huriez
🇫🇷Lille, France
CHU de Montpellier, Hopital Saint-Eloi
🇫🇷Montpellier, France
Hotel Dieu
🇫🇷Nantes, France
Hopitaux Universitaires Est Parisien Hopital Saint Antoine
🇫🇷Paris, France
Hopital de la Pitie Salpetriere
🇫🇷Paris, France
Hôpital Necker-Enfants Malades
🇫🇷Paris, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
CHU Bretonneau
🇫🇷Tours, France
Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux
🇫🇷Pessac, France
Centre Hospitalier Lyon-Sud Service d'hematologie
🇫🇷Pierre Benite, France
Chu Rennes - Hopital Pontchaillou
🇫🇷Rennes Cedex, France
CHU Poitiers - Hôpital la Milétrie
🇫🇷Poitiers, France
Universitätsklinik Carl Gustav Carus, Med. Klinik u. Poliklinik I
🇩🇪Dresden, Germany
Evangelisches Krankenhaus Essen-Werden
🇩🇪Essen, Germany
St. Barbara-Klinik Hamm GmbH
🇩🇪Hamm, Germany
Universitätsklinik Hamburg-Eppendorf UKE
🇩🇪Hamburg, Germany
Praxisklinik für Haematologie und Onkologie Koblenz
🇩🇪Koblenz, Germany
Universitaetsklinikum Koelnt
🇩🇪Koeln, Germany
Universitätsmedizin der Johannes gutenberg-Universität; III. Med. Klinik - Germany
🇩🇪Mainz, Germany
Onkologische Schwerpunkt Praxis
🇩🇪Saarbrucken, Germany
Schwarzwald-Baar Klinikum
🇩🇪Villingen-Schwenningen, Germany
Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-Germany
🇩🇪Tubingen, Germany
Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii
🇩🇪Würzburg, Germany
Alexandra General Hospital of Athens
🇬🇷Athens Attica, Greece
University of Athens - Evaggelismos Hospital (Evangelismos Hospital)
🇬🇷Athens, Greece
University Hospital Of Larissa
🇬🇷Larisa, Greece
Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Anticancer Hospital of Thessaloniki 'Theageneio'
🇬🇷Thessaloniki, Greece
Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
IRCCS Azienda Ospedaliera San Martino - IST
🇮🇹Genova, Italy
San Martino Hospital
🇮🇹Genova, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Asst Ovest Milanese - Ospedale Di Legnano
🇮🇹Legnano, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Italy
Ospedale Maggiore della Carità
🇮🇹Novara, Italy
Casa di Cura La Maddalena
🇮🇹Palermo, Italy
Ospedale Villa Sofia-Cervello
🇮🇹Palermo, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Universita Degli Studi di Roma 'Tor Vergata'
🇮🇹Roma, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS
🇮🇹Roma, Italy
ASL ROMA
🇮🇹Roma, Italy
Sapienza University of Rome
🇮🇹Roma, Italy
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
Albert Schweitzer ziekenhuis-lokatie Dordwijk
🇳🇱Dordrecht, Netherlands
Azienda Ospedaliera Santa Maria
🇮🇹Terni, Italy
Szpital Wojewodzki w Opolu
🇵🇱Opole, Poland
Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Szpital Magodent
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Ryazan Regional Clinical Hospital
🇷🇺Ryazan, Russian Federation
S.P. Botkin Moscow City Clinical Hospital
🇷🇺Moscow, Russian Federation
Emergency Hospital of Dzerzhinsk
🇷🇺Dzerzhinsk, Russian Federation
Nizhniy Novgorod Region Clinical Hospital
🇷🇺Nizhny Novgorod, Russian Federation
Inst. Cat. Doncologia-H Duran I Reynals
🇪🇸Barcelona, Spain
Clinical Research Institute of Hematology and Transfusiology
🇷🇺St-Petersburg, Russian Federation
Oncology Dispensary of Komi Republic
🇷🇺Syktyvkar, Russian Federation
Oncological dispensary #2
🇷🇺Sochi, Russian Federation
Hosp. Clinic I Provincial de Barcelona
🇪🇸Barcelona, Spain
Hosp. de Jerez de La Frontera
🇪🇸Jerez de la Frontera, Spain
Hosp. Univ. Son Espases
🇪🇸Palma, Spain
Hosp. Univ. de La Paz
🇪🇸Madrid, Spain
Hosp. Costa Del Sol
🇪🇸Malaga, Spain
Hosp. Gral. Univ. de Toledo
🇪🇸Toledo, Spain
Hosp. Univ. de Canarias
🇪🇸San Cristóbal de La Laguna, Spain
Hosp. Clinico Univ. de Salamanca
🇪🇸Salamanca, Spain
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
UZ Gent
🇧🇪Gent, Belgium