Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma.
- Conditions
- Relapsed Multiple MyelomaRefractory Multiple Myeloma
- Interventions
- Registration Number
- NCT03158688
- Lead Sponsor
- Amgen
- Brief Summary
Compare carfizomib, dexamethasone, and daratumumab (KdD) to Carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in participants with multiple myeloma who have relapsed after 1 to 3 prior therapies.
- Detailed Description
This is a phase 3 multicenter, open-label, randomized study in participants with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior therapies.
Participants receive the treatment determined by randomization for a maximum of approximately 5 years, up to 30 days prior to the final analysis data cutoff (DCO) date or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or death (whichever occurs first). No crossover between the treatment arms is allowed.
This was an open-label study. However, the assessment of response and disease progression for the primary analysis was determined by an Independent Review Committee (IRC) in a blinded manner. Sensitivity analyses of response and disease progression were determined centrally by the sponsor using a validated computer algorithm (Onyx Response Computational Assessment \[ORCA\]) in a blinded manner.
Following progression or discontinuation of study drug(s), participants will have 1 follow-up visit (30 days \[+3} after last dose of all study drug\[s\]). After disease progression, data on survival status and subsequent antimyeloma therapy will be gathered at long-term follow-up (LTFU) visits every 12 weeks (+/-2 weeks) until the Final Analysis DCO.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 466
- Criteria 1 Relapsed or progressive multiple myeloma after last treatment
- Criteria 2 Males or females ≥ 18 years of age
- Criteria 3 Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:
- IgG multiple myeloma: serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL,
- IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL,
- urine M-protein ≥ 200 mg/24 hours,
- in subjects without measurable serum or urine M- protein, serum free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
- Criteria 4 Received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy
- Criteria 5 Prior therapy with carfilzomib is allowed as long as the patient had at least a partial response (PR) to most recent therapy with carfilzomib, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and will have at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not proteasome inhibitors or CD38 antibodies during this 6-month carfilzomib treatment free interval)
- Criteria 6 Prior therapy with anti-CD38 antibodies is allowed as long as the patient had at least a PR to most recent therapy with CD38 antibody, was not removed due to toxicity, did not relapse within 60 days from intensive treatment (at least every other week) of CD38 antibody therapy, and will have at least a 6 month CD38 antibody treatment-free interval from last dose received until first study treatment
- Other inclusion criteria may apply
- Criteria 1 Waldenström macroglobulinemia
- Criteria 2 Multiple myeloma of IgM subtype
- Criteria 3 POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Criteria 4 Plasma cell leukemia (> 2.0 * 10^9/L circulating plasma cells by standard differential)
- Criteria 5 Myelodysplastic syndrome
- Criteria 6 Known moderate or severe persistent asthma within the past 2 years
- Criteria 7 Known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of predicted normal
- Criteria 8 Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization
- Other exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Kd - Carfilzomib and Dexamethasone Dexamethasone Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. Kd - Carfilzomib and Dexamethasone Carfilzomib Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. KdD - Carfilzomib, Dexamethasone and Daratumumab Dexamethasone Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg was further continued on Cycles 7+: day 1 only. KdD - Carfilzomib, Dexamethasone and Daratumumab Daratumumab Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg was further continued on Cycles 7+: day 1 only. KdD - Carfilzomib, Dexamethasone and Daratumumab Carfilzomib Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg was further continued on Cycles 7+: day 1 only.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only) From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC). The duration of PFS was right censored for participants who met any of the following conditions: 1. no baseline/post-baseline disease assessments; 2. started a new anti myeloma therapy before documentation of progressive disease or death; 3. progressive disease or death immediately after more than 70 days without disease assessment visit or; 4. alive without documentation of disease progression before the analysis trigger date (PA DCO); 5. lost to follow-up or withdrawn consent.
- Secondary Outcome Measures
Name Time Method Overall Response (OR) as Assessed by the Independent Review Committee (PA DCO Only) From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks Overall response rate was defined as the percentage of participants in each treatment group who achieve partial response (PR) or better per the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) as their best response.
Complete Response (CR): No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.
Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-component with urine M-component \<100 mg/24 hours.
Partial Response (PR): ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to \< 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
95% CIs for proportions were estimated using the Clopper-Pearson method.Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee 12 Months (8- to 13-month window) MRD\[-\]CR at 12 months was defined as achievement of CR per IMWG-URC by IRC and MRD\[-\] status as assessed by next-generation sequencing (NGS; at a 10\^-5 level) at the 12 months landmark (8 to 13 month window).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks Treatment-emergent adverse events are defined as any adverse event with an onset after the administration of the first dose of any study treatment and within the end of study or 30 days of the last dose of any study treatment, whichever occurs earlier.
The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal.
Treatment-related adverse events are treatment-emergent adverse events considered related to at least one study drug by the investigator, including those with unknown relationship.Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (PA DCO Only) From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks Time to progression was defined as the time (in months) from randomization to documented disease progression. Participants who did not have documented disease progression were censored at the date when data was last available.
Overall Survival Up to 58 months after the first participant was enrolled (at FA DCO, a median of 40.29 weeks of treatment [any study drug] in the Kd group and 79.29 weeks of treatment [any study drug] in the KdD group; FA DCO was 15 Apr 2022) Overall survival was defined as the time from randomization until death from any cause. Deaths collected via public source, after end of study were included. Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. Participants still alive were censored at the date last known to be alive.
Percentage of Participants With a Complete Response (CR) as Assessed by the Independent Review Committee (PA DCO Only) From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks The percentage of participants in each treatment group who achieved stringent complete response (sCR) or CR per IMWG-URC, as assessed by the IRC, as their best response is presented.
Time to Overall Response as Assessed by the Independent Review Committee (PA DCO Only) From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks Time to overall response was defined as the time from randomization to the earliest date a response of partial response (PR) or better as per IMWG-URC is first achieved and subsequently confirmed for participants with a best response of PR or better.
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose Baseline (Day 1 pre-dose) up to 236.3 weeks (longest treatment duration as of the FA DCO) Health-related quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality of Life Core Module (QLQ-C30) questionnaire, a validated instrument in multiple myeloma patients. Scores range from 0 to 100, with higher scores indicating better health related quality of life.
QLQ-C30 questionnaire was administered prior to dosing every 28 ± 7 days starting from cycle 1 day 1 through first follow-up visit (30 days \[+3\] after last dose of all study drugs).Kaplan-Meier Estimate for Duration of Response (DOR) (PA DCO Only) From Day 1 until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks Duration of response (DOR) was defined as the time (in months) from first evidence of partial response (PR) or better per IMWG-URC by IRC to the earlier of disease progression or death due to any cause for participants with a best response of PR or better. For those who are alive and have not experienced disease progression at the time of data cutoff for analysis, duration of response was right-censored.
Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.Kaplan-Meier Estimate for Time to Next Treatment (TTNT) PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks Time to next treatment was defined as the time (in months) from randomization to the initiation of subsequent non-protocol anti-cancer treatment for multiple myeloma. Time to next treatment for participants who do not start the subsequent treatment for multiple myeloma was censored at the date when the participant's information was last available.
Medians of TTNT duration were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks A measure of the persistence of the CR (includes strict CR) per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and MRD\[-\] status as assessed by next-generation sequencing (NGS; at a 10\^-5 level) for 12 months or more after achieving MRD\[-\]CR status.
95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only) Randomization to Months 3, 6, 12, and 18 Time to progression was defined as the time (in months) from randomization to documented disease progression. This outcome reports TTP as the percentage of participants who were event free (that is, they had not had disease progression) at the specified time frames. Independent Review Committee assessment for this outcome measure was not planned after the primary analysis.
95% CIs for event-free rates were estimated using the method by Kalbfleisch and Prentice (1980) with log-log transformation.Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months 12 Months (8- to 13-month window) MRD\[-\] at 12-month was defined as achievement of MRD\[-\] status as assessed by next-generation sequencing (NGS; at a 10\^-5 level) at the 12 months landmark (from 8 months to 13 months window).
95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.
Trial Locations
- Locations (113)
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Baylor Charles A Sammons Cancer Center at Dallas
🇺🇸Dallas, Texas, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite cedex, France
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
St Vincents Hospital Melbourne
🇦🇺Fitzroy, VIC, Victoria, Australia
Epworth Healthcare
🇦🇺East Melbourne, Victoria, Australia
Medizinische Universitaet Graz
🇦🇹Graz, Austria
Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
🇫🇷Lille Cedex, France
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Ziekenhuis Netwerk Antwerpen Stuivenberg
🇧🇪Antwerpen, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Centre Hospitalier Départemental les Oudairies
🇫🇷La Roche Sur Yon Cedex 9, France
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
St Vincents Hospital Sydney
🇦🇺St Leonards, New South Wales, Australia
Universitair Ziekenhuis Brussel
🇧🇪Brussel, Belgium
Centre Hospitalier de Versailles - Hopital Andre Mignot
🇫🇷Le Chesnay cedex, France
Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie
🇫🇷Poitiers Cedex, France
Theagenion Cancer Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Landeskrankenhaus Salzburg
🇦🇹Salzburg, Austria
Fakultni nemocnice Ostrava
🇨🇿Ostrava-Poruba, Czechia
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
Centre Hospitalier Universitaire de Nancy - Hopital de Brabois
🇫🇷Vandoeuvre les Nancy Cedex, France
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Fakultni nemocnice Plzen
🇨🇿Plzen, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Nagoya City University Hospital
🇯🇵Nagoya-shi, Aichi, Japan
Centre Hospitalier Universitaire de Bordeaux - Hopital Haut Leveque
🇫🇷Pessac Cedex, France
Christie Hospital
🇬🇧Manchester, United Kingdom
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
🇭🇺Szeged, Hungary
Tokushima Prefectural Central Hospital
🇯🇵Tokushima-shi, Tokushima, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hacettepe Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Cataluña, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Cataluña, Spain
University College London Hospital
🇬🇧London, United Kingdom
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Castilla León, Spain
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
New York Presbyterian Hospital, Weill Cornell Medical College
🇺🇸New York, New York, United States
Lynn Cancer Center Boca Raton Regional Hospital, Lynn Cancer Institute
🇺🇸Boca Raton, Florida, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
Hattiesburg Clinic Hematology/Oncology
🇺🇸Hattiesburg, Mississippi, United States
Gabrail Cancer Center, LLC
🇺🇸Dover, Ohio, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
National Hospital Organization Okayama Medical Center
🇯🇵Okayama-shi, Okayama, Japan
Kyushu University Hospital
🇯🇵Fukuoka-shi, Fukuoka, Japan
Gunma University Hospital
🇯🇵Maebashi-shi, Gunma, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto-shi, Kyoto, Japan
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich w Chorzowie
🇵🇱Chorzow, Poland
SBHI of Nizhny Novgorod region Regional Clinical Hospital of Nizhny Novgorod na N A Semashko
🇷🇺Nizhny Novgorod, Russian Federation
Profesor Dr Ion Chiricuta Institut of Oncology
🇷🇴Cluj-Napoca, Romania
Ege University Faculty of Medicine
🇹🇷Izmir, Turkey
University of Chicago Medical Center - Multiple Myeloma Research Consortium
🇺🇸Chicago, Illinois, United States
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi
🇹🇷Ankara, Turkey
Ondokuz Mayis Universitesi Tip Fakultesi
🇹🇷Samsun, Turkey
St James University Hospital
🇬🇧Leeds, United Kingdom
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
🇭🇺Budapest, Hungary
General Hospital Evangelismos
🇬🇷Athens, Greece
Tesshokai Kameda General Hospital
🇯🇵Kamogawa-shi, Chiba, Japan
Specialized Hospital for Active Treatment of Hematology Diseases EAD
🇧🇬Sofia, Bulgaria
General University Hospital of Patras Panagia i Voithia
🇬🇷Patra, Greece
Barwon Health, University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Centrum Onkologii Ziemi Lubelskiej im Swietego Jana z Dukli
🇵🇱Lublin, Poland
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
🇧🇬Plovdiv, Bulgaria
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
🇧🇬Sofia, Bulgaria
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Niigata, Japan
Saitama Medical Center
🇯🇵Kawagoe-shi, Saitama, Japan
InterHem
🇵🇱Bialystok, Poland
Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Bucharest Emergency University Hospital
🇷🇴Bucuresti, Romania
Coltea Clinical Hospital
🇷🇴Bucharest, Romania
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Royal Brisbane and Womens Hospital
🇦🇺Herston, Queensland, Australia
Centre Hospitalier Universitaire de Nantes
🇫🇷Nantes Cedex 1, France
Alexandra Hospital
🇬🇷Athens, Greece
Bekes Megyei Kozponti Korhaz Dr Rethy Pal Tagkorhaz
🇭🇺Bekescsaba, Hungary
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka-shi, Fukuoka, Japan
National Hospital Organization Shibukawa Medical Center
🇯🇵Shibukawa-shi, Gunma, Japan
Tochigi Cancer Center
🇯🇵Utsunomiya-shi, Tochigi, Japan
Cancer Institute Hospital of Japanese Foundation for Cancer Research
🇯🇵Koto-ku, Tokyo, Japan
Policlinica de Diagnostic Rapid
🇷🇴Brasov, Romania
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Toyohashi Municipal Hospital
🇯🇵Toyohashi-shi, Aichi, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki-shi, Gifu, Japan
Osaka University Hospital
🇯🇵Suita-shi, Osaka, Japan
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Spitalul Clinic Municipal Filantropia Craiova
🇷🇴Craiova, Romania
SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov
🇷🇺Petrozavodsk, Russian Federation
State Budget Educational Institution of High Professional Skills Samara State Medical University
🇷🇺Samara, Russian Federation
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
Spitalul Clinic Colentina
🇷🇴Bucuresti, Romania
Clinic of professional pathology and hematology
🇷🇺Saratov, Russian Federation
Japanese Red Cross Medical Center
🇯🇵Shibuya-ku, Tokyo, Japan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Charleston Oncology
🇺🇸Charleston, South Carolina, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia