Phase 3 Study With Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed Multiple Myeloma Patients

Phase 3

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: Bortezomib; Drug: Carfilzomib; Drug: Dexamethasone

• Registration Number: NCT01568866
• Lead Sponsor: Amgen

Brief Summary

The primary objective of this study was to compare progression-free survival in patients with multiple myeloma who relapsed after 1 to 3 prior therapies treated with carfilzomib plus dexamethasone or bortezomib plus dexamethasone.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-03-28
• Study First Submitted QC: 2012-03-30
• Study First Posted: 2012-04-02
• Study Start: 2012-06-20
• Primary Completion: 2014-11-10
• Results First Submitted: 2015-11-06
• Results First Submitted QC: 2015-11-06
• Results First Posted: 2015-12-11
• Study Completion: 2018-02-05
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-10
• Last Update Posted: 2022-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 929

Inclusion Criteria

1. Multiple myeloma with relapsing or progressing disease at study entry.

2. Patients must have evaluable multiple myeloma with, at least one of the following (assessed within 21 days prior to randomization):

   • Serum M-protein ≥ 0.5 g/dL, or
   • Urine M-protein ≥ 200 mg/24 hour, or
   • In patients without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lamda ratio, or
   • For immunoglobulin (Ig) A patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL).

3. Patients must have documented at least partial response (PR) to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.

4. Received 1, but no more than 3 prior treatment regimens or lines of therapy for multiple myeloma. (Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as one line of therapy).

5. Prior therapy with Velcade is allowed as long as the patient had at least a PR to prior Velcade therapy, was not removed from Velcade therapy due to toxicity, and will have at least a 6 month Velcade treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month Velcade treatment-free interval).

6. Prior therapy with carfilzomib is allowed as long as the patient had at least a PR to prior carfilzomib therapy, was not removed from carfilzomib therapy due to toxicity, and had 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 in the proteasome inhibitor class during this 6 month carfilzomib treatment-free interval). The exception to this is patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial.

7. Males and females ≥ 18 years of age.

8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

9. Adequate hepatic function within 21 days prior to randomization, with bilirubin < 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN.

10. Left ventricular ejection fraction (LVEF) ≥ 40%.

11. Absolute neutrophil count (ANC) ≥ 1000/mm³ within 21 days prior to randomization. Screening ANC should be independent of growth factor support for ≥ 1 week.

12. Hemoglobin ≥ 8.0 g/dL within 21 days prior to randomization. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed, however most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.

13. Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ if myeloma involvement in the bone marrow is > 50%) within 21 days prior to randomization. Patients should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count.

14. Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min within 21 days prior to randomization. Calculation should be based on standard formula such as the Cockcroft and Gault:

    [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female.

15. Written informed consent in accordance with federal, local, and institutional guidelines.

16. Female patients of child-bearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to randomization and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

17. Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP.

Exclusion Criteria

1. Multiple Myeloma of IgM subtype.

2. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.

3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).

4. Plasma cell leukemia or circulating plasma cells ≥ 2 × 10^9/L.

5. Waldenstrom's Macroglobulinemia.

6. Patients with known amyloidosis.

7. Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to randomization.

8. Patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial.

9. Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow).

10. Immunotherapy within 21 days prior to randomization.

11. Major surgery (excluding kyphoplasty) within 28 days prior to randomization.

12. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to randomization.

13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to randomization.

14. Known human immunodeficiency (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).

15. Patients with known cirrhosis.

16. Second malignancy within the past 3 years except:

    • adequately treated basal cell or squamous cell skin cancer
    • carcinoma in situ of the cervix
    • prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
    • breast carcinoma in situ with full surgical resection
    • treated medullary or papillary thyroid cancer

17. Patients with myelodysplastic syndrome.

18. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to randomization.

19. Female patients who are pregnant or lactating.

20. Known history of allergy to Captisol(a cyclodextrin derivative used to solubilize carfilzomib).

21. Patients with hypersensitivity to carfilzomib, Velcade, boron, or mannitol.

22. Patients with contraindication to dexamethasone.

23. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.

24. Ongoing graft-vs-host disease.

25. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bortezomib plus Dexamethasone	Bortezomib	Participants received bortezomib 1.3 mg/m² administered IV or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Bortezomib plus Dexamethasone	Dexamethasone	Participants received bortezomib 1.3 mg/m² administered IV or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Carfilzomib plus Dexamethasone	Carfilzomib	Participants received 20 mg/m² carfilzomib administered by intravenous (IV) infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Carfilzomib plus Dexamethasone	Dexamethasone	Participants received 20 mg/m² carfilzomib administered by intravenous (IV) infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	From randomization until the data cut-off date of 10 November 2014; median follow-up time for PFS was 11.1.and 11.9 months in the bortezomib and carfilzomib arms respectively	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).; Median PFS was estimated using the Kaplan-Meier method. Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From randomization until the data cut-off date of 03 January 2017; median follow-up time for OS was 36.9 and 37.5 months for each treatment group respectively.	Overall survival (OS) is defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at the patient's date of last contact (last known to be alive).; Median overall survival was estimated using the Kaplan-Meier method.
Overall Response	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group.	Disease response was evaluated according to the IMWG-URC by the IRC. Overall response was defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR) or stringent CR (sCR).; sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).; CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein \<100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.; 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.
Duration of Response	From randomization until the data cut-off date of 10 November 2014; median follow-up time for DOR was 9.4 and 10.4 months for each treatment group respectively.	Duration of response (DOR) was calculated for participants who achieved an sCR, CR, VGPR, or PR. Duration of response is defined as the time from first evidence of PR or better to confirmation of disease progression or death due to any cause. Median duration of response was estimated using the Kaplan-Meier method. Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy	From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group.	Neuropathy events were defined as Grade 2 or higher peripheral neuropathy as specified by peripheral neuropathy Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query, narrow (scope) (SMQN) terms.; Peripheral neuropathy was assessed by neurologic exam and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1: Asymptomatic; Grade 2: Moderate symptoms, limiting instrumental activities of daily living (ADL) Grade 3: Severe symptoms; limiting self-care ADL; Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death.
Percentage of Participants With a Significant Reduction in Left Ventricular Ejection Fraction (LVEF)	Baseline and 24 weeks	A significant reduction in LVEF was defined as a ≥ 10% decrease (absolute change) from baseline in participants whose baseline LVEF is ≤ 55%.; For participants with LVEF \> 55% at baseline, a significant change was defined as a decrease in LVEF to \< 45%.
Change From Baseline in Right Ventricular Fractional Area Change (FAC)	Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group).	Right ventricular function was assessed by measuring fractional area change (FAC) on echocardiogram.
Change From Baseline in Pulmonary Artery Systolic Pressure (PASP)	Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group).	Pulmonary artery pressure was measured using transthoracic echocardiogram.

Trial Locations

Locations (241)

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Gabrail Cancer Center; 🇺🇸 Canton, Ohio, United States

Saint John Regional Hospital; 🇨🇦 Saint John, New Brunswick, Canada

University College Hospital; 🇬🇧 London, England, United Kingdom

Hematology Oncology of Indiana, PC; 🇺🇸 Indianapolis, Indiana, United States

Western Pennsylvania Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

The Methodist Cancer Center; 🇺🇸 Houston, Texas, United States

Ziekenhuis Netwerk Antwerpen; 🇧🇪 Antwerp, Belgium

Providence St. Joseph Medical Center; 🇺🇸 Burbank, California, United States

Scott & White Memorial Hospital; 🇺🇸 Temple, Texas, United States

St. Vincent's Public Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

Hematology/Oncology Associates of SC; 🇺🇸 Greenville, South Carolina, United States

MAB Oncology/Hematology; 🇺🇸 Melbourne, Florida, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

Western Hospital; 🇦🇺 Footscray, Victoria, Australia

UCSD Moore Cancer Center; 🇺🇸 La Jolla, California, United States

Haematology and Oncology Clinics of Australia at Wesley; 🇦🇺 South Brisbane, Queensland, Australia

Saint George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Sunshine Hospital; 🇦🇺 St. Albans, Victoria, Australia

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Palm Beach Cancer Institute; 🇺🇸 West Palm Beach, Florida, United States

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

Krankenhaus der Elisabethinen Linz, I Interne Abteilung; 🇦🇹 Linz, Upper Austria, Austria

Royal Brisbane and Women's Hospital; 🇦🇺 Herston, Queensland, Australia

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

Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro; 🇧🇷 Rio de Janeiro, Brazil

Hemocentro Campinas-Unicamp; 🇧🇷 Campinas, SAO Paulo, Brazil

Haematology and Oncology Clinics of Australia at Chermside; 🇦🇺 South Brisbane, Queensland, Australia

Universitair Ziekenhuis Leuven; 🇧🇪 Leuven, Flemish Brabant, Belgium

Bács-Kiskun Megyei Kórház Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza; 🇭🇺 Kecskemét, Bacs-kiskun, Hungary

Fakultní nemocnice Hradec Králové; 🇨🇿 Hradec Kralové, Vychodocesky KRAJ, Czechia

Universitätsklinikum Aachen; 🇩🇪 Aachen, Nordrhein-westfalen, Germany

Hôpital Saint-Antoine; 🇫🇷 Paris, Ile-de-france, France

Szegedi Tudományegyetem; 🇭🇺 Szeged, Csongrad, Hungary

Všeobecná fakultní nemocnice v Praze; 🇨🇿 Praha, Czechia

Clínica de Oncologia de Porto Alegre; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Universitair Ziekenhuis Gent; 🇧🇪 Ghent, Oost-vlaanderen, Belgium

Hôpital Claude Huriez; 🇫🇷 Lille Cedex, NORD Pas-de-calais, France

Pécsi Tudományegyetem; 🇭🇺 Pécs, Baranya, Hungary

Military Medical Academy Hospital for Active Treatment; 🇧🇬 Sofia, Sofiya, Bulgaria

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Sachsen, Germany

FN Ostrava; 🇨🇿 Ostrava, Severomoravsky KRAJ, Czechia

Fakultní nemocnice Brno; 🇨🇿 Brno, Czechia

Alexandra General Hospital; 🇬🇷 Athens, Attica, Greece

Debreceni Egyetem Klinikai Központ; 🇭🇺 Debrecen, Hajdu-bihar, Hungary

The Chaim Sheba Medical Center at Tel Hashomer; 🇮🇱 Tel Hashomer, Israel

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Niedersachsen, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Baden-wuerttemberg, Germany

Fakultní nemocnice Královské Vinohrady; 🇨🇿 Praha 10, Praha, Czechia

Multiprofile Hospital for Active Treatment, "Sveta Marina''; 🇧🇬 Varna, Bulgaria

Hôpital Hôtel-Dieu; 🇫🇷 Nantes cedex 1, PAYS DE LA Loire, France

Instituto Nacional do Câncer-INCA; 🇧🇷 Rio de Janeiro, Brazil

Shato, Ead; 🇧🇬 Sofia, Sofiya, Bulgaria

Instituto Centros Oncológicos Integrados de Educação e Pesquisa; 🇧🇷 Rio de Janeiro, Brazil

The Ottawa Hospital Regional Cancer Centre; 🇨🇦 Ottawa, Ontario, Canada

Centre Henri-Becquerel; 🇫🇷 Rouen Cedex 1, Haute-normandie, France

Universitätsklinikum Ulm; 🇩🇪 Ulm, Baden-wuerttemberg, Germany

Hopital Maisonneuve-Rosemont; 🇨🇦 Montréal, Quebec, Canada

Klinikum Chemnitz gGmbH; 🇩🇪 Chemnitz, Sachsen, Germany

Centre Hospitalier Universitaire Brest; 🇫🇷 Brest Cedex, Bretagne, France

Medizinische Klinik der Universität Würzburg; 🇩🇪 Würzburg, Bayern, Germany

Somogy Megyei Kaposi Mac okato Korhoz; 🇭🇺 Kaposvár, Hungary

Hôpital Saint Louis; 🇫🇷 Paris, Ile-de-france, France

Azienda Policknico Umberto l di Roma; 🇮🇹 Roma, Italy

Khmelnytsky Regional Hospital, Department of Hematology; 🇺🇦 Khmelnytsky, Ukraine

Royal Marsden Hospital; 🇬🇧 Surrey, England, United Kingdom

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Hospital São Lucas da PUCRS; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Fremantle Hospital; 🇦🇺 Fremantle, Western Australia, Australia

Liga Norte Riograndense Contra o Câncer; 🇧🇷 Natal, RIO Grande DO Norte, Brazil

Cliniques Universitaires UCL de Mont-Godinne; 🇧🇪 Yvoir, Namur, Belgium

Universitätsklinikum des Saarlandes; 🇩🇪 Homburg / Saar, Saarland, Germany

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Vanderbilt Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

University of Utah School of Medicine; 🇺🇸 Salt Lake City, Utah, United States

Windsor Regional Hospital; 🇨🇦 Windsor, Ontario, Canada

Centre Hospitalier de Versailles; 🇫🇷 Le Chesnay, Ile-de-france, France

Universitatsklinikum Freiburg; 🇩🇪 Freiburg, Germany

Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

Universitätsklinikum Carl Gustav Carus, Med. Klinik und Poliklinik I; 🇩🇪 Dresden, Sachsen, Germany

Somogy Megyei Kaposi Mór Oktató Kórház; 🇭🇺 Kaposvár, Hungary

Central Coast Medical Oncology Group; 🇺🇸 Santa Maria, California, United States

Associates in Oncology/Hematology PC; 🇺🇸 Rockville, Maryland, United States

Hackensack University Medical Ctr; 🇺🇸 Hackensack, New Jersey, United States

Clinical Research Alliance Inc.; 🇺🇸 New York, New York, United States

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

Haematology & Oncology Clinics of Australia; 🇦🇺 South Brisbane, Queensland, Australia

Royal North Shore Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

The Queen Elizabeth Hospital; 🇦🇺 Woodville, South Australia, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Tokushima Prefectural Central Hospital; 🇯🇵 Tokushima, Japan

Saint Vincent's Hospital; 🇦🇺 East Melbourne, Victoria, Australia

Wilhelminenspital der Stadt Wien; 🇦🇹 Wien, Vienna, Austria

Universitair Ziekenhuis Brussel; 🇧🇪 Brussels, Belgium

Irmandade da Santa Casa de Misericórdia de São Paulo; 🇧🇷 São Paulo, Brazil

British Columbia Cancer Agency; 🇨🇦 Kelowna, British Columbia, Canada

University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD; 🇧🇬 Plovdiv, Bulgaria

Fakultní nemocnice Olomouc; 🇨🇿 Olomouc, Severomoravsky KRAJ, Czechia

Centre Hospitalier de la Cote Basque; 🇫🇷 Bayonne, Aquitaine, France

Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou; 🇫🇷 Rennes Cedex 9, Bretagne, France

Hopital Hotel-Dieu - Service d'Hematologie; 🇫🇷 Nantes, Cedex 1, France

Institut Paoli Calmettes; 🇫🇷 Marseille Cedex 9, Provence Alpes COTE D'azur, France

Universitätsklinik Heidelberg; 🇩🇪 Heidelberg, Baden-wuerttemberg, Germany

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Bénite Cedex, Rhone-alpes, France

Universitätsklinikum Münster; 🇩🇪 Münster, Nordrhein-westfalen, Germany

Egyesített Szent István és Szent László Kórház-Rendelointézet; 🇭🇺 Budapest, Hungary

Universitätsklinikum Jena; 🇩🇪 Jena, Thuringen, Germany

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Rambam Health Corp.; 🇮🇱 Haifa, Israel

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture; 🇮🇹 Rionero in Vulture, Potenza, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona; 🇮🇹 Ancona, Italy

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi; 🇮🇹 Bologna, Italy

Azienda Ospedaliero-Univesitaria San Luigi Gonzaga; 🇮🇹 Orbassano, Torino, Italy

Azienda Ospedaliera Universitaria Maggiore della Carità; 🇮🇹 Novara, Italy

Azienda Ospedaliera Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

IRCCS Azienda Ospedaliera Universitaria San Martino; 🇮🇹 Genova, Italy

Nagoya City University Hospital; 🇯🇵 Nagoya City, Aichi, Japan

Aienda Policknico Umberto I di Roma; 🇮🇹 Roma, Italy

Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto; 🇮🇹 Piacenza, Italy

Azienda Ospedaliera Universitaria Senese - Policlinico S. Maria alle Scotte; 🇮🇹 Siena, Italy

Azienda Ospedaliera Pisana Ospedale Santa Chiara; 🇮🇹 Pisa, Italy

Ogaki Municipal Hospital; 🇯🇵 Ogaki City, Gifu, Japan

Università Tor Vergata Ospedale Sant Eugenio; 🇮🇹 Roma, Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino; 🇮🇹 Torino, Italy

Toyohashi Municipal Hospital; 🇯🇵 Toyohashi, Aichi, Japan

National Hospital Organization Kyushu Cancer Center; 🇯🇵 Fukuoka-city, Fukuoka, Japan

National Hospital Organization Nishigunma National Hospital; 🇯🇵 Shibukawa, Gunma, Japan

Gunma University Hospital; 🇯🇵 Maebashi, Gunma, Japan

Sapporo Medical University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Osaka University Hospital; 🇯🇵 Suita, Osaka, Japan

Niigata Cancer Center Hospital; 🇯🇵 Niigata-city, Niigata, Japan

Tokai University Hospital; 🇯🇵 Isehara, Kanagawa, Japan

Saitama Medical Center; 🇯🇵 Kawagoe, Saitama, Japan

Tochigi Cancer Center; 🇯🇵 Utsunomiya, Tochigi, Japan

National Cancer Center Hospital; 🇯🇵 Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital Of Japanese Foundation For Cancer Research; 🇯🇵 Koto-ku, Tokyo, Japan

Tokyo Medical University Hospital; 🇯🇵 Shinjuku, Tokyo, Japan

National Hospital Organization Disaster Medical Center; 🇯🇵 Tachikawa, Tokyo, Japan

Social Insurance Kyoto Hospital of All Japan Federation of Social Insurance Associations; 🇯🇵 Kyoto, Japan

University Hospital, Kyoto Prefectural University of Medicine; 🇯🇵 Kyoto, Japan

Japanese Red Cross Medical Center; 🇯🇵 Tokyo, Japan

National Hospital Organization Okayama Medical Center; 🇯🇵 Okayama, Japan

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

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

Gachon University Gil Medical Center; 🇰🇷 Incheon, Gyeonggi-Do, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Gyeongsangnam-Do, Korea, Republic of

Kyungpook National University Hospital; 🇰🇷 Daegu, Korea, Republic of

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

National Institute of Cancer, Oncohematology Department; 🇺🇦 Kiev, Ukraine

Seoul Saint Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

North Shore Hospital; 🇳🇿 North Shore City, Auckland, New Zealand

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

Middlemore Hospital; 🇳🇿 Otahuhu, Auckland, New Zealand

Dunedin Hospital; 🇳🇿 Dunedin, New Zealand

Christchurch Hospital; 🇳🇿 Christchurch, New Zealand

Auckland City Hospital; 🇳🇿 Grafton, Aukland, New Zealand

Specjalistyczny Szpital Miejski im. Mikolaja Kopernika; 🇵🇱 Torun, Kujawsko-Pomorskie, Poland

Zamojski Szpital Niepubliczny Sp. z o.o.; 🇵🇱 Zamosc, Lubelskie, Poland

Szpital Uniwersytecki w Krakowie; 🇵🇱 Krakow, Malopolskie, Poland

Instytut Hematologii i Transfuzjologii; 🇵🇱 Warszawa, Mazowieckie, Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K. Marcinkowskiego w Poznaniu; 🇵🇱 Poznan, Wielkopolskie, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Pomorskie, Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól Szpitali Miejskich; 🇵🇱 Chorzów, Slaskie, Poland

Spitalul Universitar de Urgenta Bucuresti; 🇷🇴 Bucharest, Bucuresti, Romania

Policlinica de Diagnostic Rapid SA, Compartiment Medical Oncologie-Hematologie; 🇷🇴 Brasov, Romania

Institutul Clinic Fundeni; 🇷🇴 Bucuresti, Romania

Republican Clinical Hospital #1; 🇷🇺 Izhevsk, Russian Federation

Non-state Healthcare Institution "N.A. Semashko Central Clinical Hospital #2 of JSC "Russian Railway; 🇷🇺 Moscow, Russian Federation

City Clinical Hospital n.a. S. P. Botkin; 🇷🇺 Moscow, Russian Federation

Clinical Hospital Number 31; 🇷🇺 Saint Petersburg, Russian Federation

Ryazan Regional Clinical Hospital; 🇷🇺 Ryazan, Russian Federation

National University Cancer Institute; 🇸🇬 Singapore, Singapore

First Saint Petersburg I.P. Pavlov State Medical University; 🇷🇺 Saint Petersburg, Russian Federation

GUZ Samara Regional Clinical Hospital n.a. M.I. Kalinin; 🇷🇺 Samara, Russian Federation

Singapore General Hospital; 🇸🇬 Singapore, Singapore

Singapore Oncology Consultants; 🇸🇬 Singapore, Singapore

Hospital Son Llàtzer; 🇪🇸 Palma de Mallorca, Baleares, Spain

Univerzitná nemocnica Bratislava; 🇸🇰 Bratislava, Slovakia

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital Clinic I Provincial de Barcelona; 🇪🇸 Barcelona, Spain

Institut Universitari Dexeus; 🇪🇸 Barcelona, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro; 🇪🇸 Madrid, Spain

Hospital Universitario La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital Clínico Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitari i Politecnic La Fé de Valencia; 🇪🇸 Valencia, Spain

Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

National Cheng-Kung University Hospital; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Medical Foundation-LinKou Branch; 🇨🇳 Tao-Yuan, Taiwan

Khmelnytsky Regional Clinical Hospital; 🇺🇦 Khmelnytsky, Ukraine

Ramathibodi Hospital; 🇹🇭 Bangkok, Bangkok Metropolis, Thailand

Srinagarind Hospital; 🇹🇭 Khon Kaen, Thailand

Municipal Institution of Health Protection "Clinical Hospital #8"; 🇺🇦 Kharkov, Kharkiv, Ukraine

Cherkassy Regional Oncology Center; 🇺🇦 Cherkassy, Ukraine

Institute of Urgent and Reparative Surgury of Ukraine Academy of Medical Sciences; 🇺🇦 Donetsk, Ukraine

Kyiv Bone Marrow Transplantation Center; 🇺🇦 Kyiv, Ukraine

Regional Clinical Hospital; 🇺🇦 Mykolayiv, Ukraine

Lviv Regional Oncology Dispensary; 🇺🇦 Lviv, Ukraine

Lviv State Oncology Regional Treatment-Prophylactic Center, Department of Chemotherapy; 🇺🇦 Lviv, Ukraine

Royal Free Hospital; 🇬🇧 London, England, United Kingdom

Manchester Royal Infirmary; 🇬🇧 Manchester, England, United Kingdom

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, England, United Kingdom

Derriford Hospital; 🇬🇧 Plymouth, England, United Kingdom

Royal Hallamshire Hospital; 🇬🇧 Sheffield, England, United Kingdom

Royal Wolverhampton Hospitals Trust; 🇬🇧 Wolverhampton, England, United Kingdom

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Kobe City Medical Center General Hospital; 🇯🇵 Kobe, Hyogo, Japan

Queen Elizabeth II Health Science Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Universitätsmedizin der Johannes Gutenberg Universität; 🇩🇪 Mainz, Rheinland-pfalz, Germany

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

Kyushu University Hospital; 🇯🇵 Fukuoka, Japan

FGU Russian Scientific Research Institute of Hematology and Transfusiology; 🇷🇺 Saint Petersburg, Russian Federation

Federal Almazov Medical Research Centre; 🇷🇺 Saint Petersburg, Russian Federation

Churchill Hospital; 🇬🇧 Oxford, England, United Kingdom

Toranornon Hospital; 🇯🇵 Shinagawa, Tokyo, Japan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

King Chulalongkorn Memorial Hospital; 🇹🇭 Bangkok, Bangkok Metropolis, Thailand

Spitalul Clinic Judetean de Urgenta Brasov (Bumbea, Horia); 🇷🇴 Brasov, Romania

Institutul Regional de Oncologie Iasi; 🇷🇴 Iasi, Romania

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

City Hematology Center; 🇺🇦 Dnepropetrovsk, Dnipropretrovsk, Ukraine

MI "Dnipropetrovsk City Multifield Clinical Hospital #4" of Dnipropetrovsk Regional Council", City Hematology Center; 🇺🇦 Dnipropetrovsk, Ukraine

Cliniques Universitaires Saint Luc; 🇧🇪 Brussels, Belgium

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

Wake Forest University Health Sciences, Section on Hematology and Oncology; 🇺🇸 Winston-Salem, North Carolina, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

University of Kansas; 🇺🇸 Kansas City, Missouri, United States

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

Medizinische Universität Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria