A Study of Ixazomib, Given With Dexamethasone in Adults With Multiple Myeloma
- Conditions
- Relapsed and/or Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT03170882
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
The main aim of this study is to learn if ixazomib, given with dexamethasone, stops the cancer from getting worse in people with relapsed or refractory multiple myeloma. It will be compared to another medicine called pomalidomide, given with dexamethasone with people with the same condition. Relapsed means the previous cancer treatment stopped working, over time. Refractory means they did not respond to previous cancer treatment. Another aim is to check for side effects from the study medicines.
At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance.
* Ixazomib capsules, given with dexamethasone tablets
* Pomalidomide capsules, given with dexamethasone tablets
All participants will take their study medicine on specific days during a 28-day cycle.
The 1st dose of study medicines in each 28-day cycle will take place in the clinic, The other doses of the study medicines will be taken at home. This will happen for 6 cycles. After this, all study medicines will be taken at home.
After treatment, participants will visit the clinic every 12 weeks for a check-up.
If participants cannot attend their clinic for an important reason (for example, due to the COVID-19 pandemic), the clinic will make alternative arrangements using their local procedures.
- Detailed Description
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (RRMM). This study will compare the efficacy and safety in participants who take ixazomib and dexamethasone to pomalidomide and dexamethasone. It is an open-label, Phase 2 study.
The study will enroll approximately 120 participants. Participants will receive:
* Ixazomib 4 mg + dexamethasone 20 mg (or 10 mg if participant is aged \>=75 years) OR
* Pomalidomide 4 mg + dexamethasone 40 mg (or 20 mg if participant is aged \>=75 years)
All participants will be asked to take either ixazomib plus dexamethasone (in cases where only 4 mg tablets for dexamethasone are available, the following dexamethasone schedule is recommended for participants aged \>=75 years: 12 mg dexamethasone will be given on Days 1, 8, 15, and 22 of every 28-day cycle; and 8 mg dexamethasone will be given on Days 2, 9, 16, and 23 of every 28-day cycle) or pomalidomide 4 mg + dexamethasone 40 mg at recommended doses.
This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 28 months after the first participant enters the study.
Participants will make multiple visits to the clinic, and will be contacted for progression free-survival (PFS) follow-up, in case of study drug discontinuation for up to 4 years from first dose administration. After disease progression, participants will be followed-up for overall survival (OS) every 12 weeks until death or up to 4 years.
Alternative methods for administering study procedures/assessments may be considered when it is not possible for the participants to come to the study site due to extenuating circumstances (e.g., due to the COVID-19 pandemic).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 122
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Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to International Myeloma Working Group (IMWG) criteria.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
-
Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had.
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Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
-
Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either:
- Achieved at least a partial response (PR) and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR
- Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related adverse events [AEs] before completion of the planned treatment course) without PD before the start of the next regimen.
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Must have measurable disease defined by:
- Serum M-protein >=1 g/dL (>=10 g/L), OR
- Urine M-protein >=200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
-
Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
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Recovered (that is, less than or equal to [<=] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
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Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies [REMS], pregnancy prevention programs).
- Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy- unless the autologous SCT was performed a year or more before disease progression.
- Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
- Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
- Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization (Note: "spot" radiation for areas of pain is permitted), and major surgery within 14 days before randomization.
- Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
- Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
- Central nervous system involvement with MM (by clinical symptoms and signs).
- Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic acid (RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive.
- Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization.
- Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
- History of severe cutaneous reactions, including hypersensitivity reactions such as Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), in the context of treatment with lenalidomide or thalidomide.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pomalidomide 4 mg + Dexamethasone 40 mg Dexamethasone Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged \>=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years. Pomalidomide 4 mg + Dexamethasone 40 mg Pomalidomide Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged \>=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years. Ixazomib 4 mg + Dexamethasone 20 mg Ixazomib Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged \>=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years. Ixazomib 4 mg + Dexamethasone 20 mg Dexamethasone Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged \>=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years) PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of \>=25 % from nadir in: Serum M component (increase must be \>=0.5 gram per deciliter \[g/dl\]); Urine M-component (increase must be \>=200 milligram \[mg\]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: bone marrow plasma cell percentage must be \>=10%; Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia (\>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From date of randomization to death due to any cause (Up to approximately 3 years) OS was defined as the time from randomization to death from any cause, up to 3 years are reported.
Percentage of Participants With Overall Response From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years) Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when baseline value \>=30% and; if present at baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; \<5 % plasma cells in bone marrow.
Duration of Response (DOR) From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years) DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. Per IMWG criteria, PR:\>=50% reduction of serum M protein+reduction in 24-hour urinary M protein by \>=90% to \<200 mg/24-hour or \>=50% decrease in difference between involved and uninvolved FLC levels/ \>=50% reduction in bone marrow plasma cells, if \>=30% at Baseline/ \>=50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR:negative immunofixation on serum + urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. PD:serum M-component increase \>=0.5 g/dl or urine M-component increase \>=200 mg/24-hour/ difference between involved and uninvolved FLC levels increase \>10 mg/dl or bone marrow plasma cell \>=10%/development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.
Time to Response From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years) Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M-protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when Baseline value \>=30% and; if present at Baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; \<5% plasma cells in bone marrow.
Time to Progression (TTP) From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years) TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of \>=25% from nadir in: Serum M-component (increase must be \>=0.5 g/dl; Urine M-component (increase must be \>=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be \>=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (\>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.
Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning.
HRQOL Based on EORTC QLQ-C30 SubScale Score Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7.
HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology.
Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score End of Treatment (Up to 28 cycles, each cycle was of 28 days) EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions.
HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life.
Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter Up to approximately 3 years Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).
HU: Duration of Medical Encounters Up to approximately 3 years Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).
Trial Locations
- Locations (111)
Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Lakeridge Health Center
🇨🇦Ottawa, Ontario, Canada
Universitatsklinikum Tubingen
🇩🇪Tubingen, Germany
Aalborg Universitetshospital
🇩🇰Aalborg, Nordjylland, Denmark
AZ St Jan Brugge Oostende AV
🇧🇪Brugge, Belgium
University General Hospital of Ioannina
🇬🇷Ioannina, Greece
Theageneio Anticancer Oncology Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Ospedale Santa Maria Delle Croci
🇮🇹Ravenna, Emilia-Romagna, Italy
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
🇮🇹Brescia, Italy
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
🇮🇹Meldola, Italy
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Groupe Hospitalier du Havre
🇫🇷Montivilliers, Seine-Maritime, France
CHU Amiens Hopital Sud
🇫🇷Amiens, France
CHRU Nancy
🇫🇷Vandoeuvre Les Nancy, Meurthe-et-Moselle, France
CHRU de Brest - Hopital Morvan
🇫🇷Brest, Finistere, France
Centre Hospitalier Bretagne Atlantique Vannes
🇫🇷Vannes, Morbihan, France
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
University General Hospital of Patras
🇬🇷Patra, Achaia, Greece
University Hospital of Alexandroupolis
🇬🇷Alexandroupoli, Greece
Evangelismos General Hospital of Athens
🇬🇷Athens, Greece
Alexandra Hospital
🇬🇷Athens, Greece
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
🇮🇹Orbassano, Piemonte, Italy
Rambam Health Corporation
🇮🇱Haifa, Israel
Centro Di Riferimento Oncologico Della Basilicata
🇮🇹Rionero in Vulture, PZ, Italy
Centre Hospitalier Fleyriat
🇫🇷Bourg-en- Bresse Cedex, France
Soroka University Medical Centre
🇮🇱Beer Sheva, Israel
Kirov Research Institute of Haematology and Blood Transfusion
🇷🇺Kirov, Russian Federation
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Sodra Alvsborgs Sjukhus Boras
🇸🇪Boras, Sweden
Azienda ULSS 6 Vicenza
🇮🇹Vicenza, Italy
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷Izmir, Turkey
Hospital Universitari de Girona Dr Josep Trueta
🇪🇸Girona, Spain
Betsi Cadwaladr University Health Board
🇬🇧Bodelwyddan, Denbighshire-SirDdinbych, United Kingdom
Stavanger Universitetssykehus
🇳🇴Stavanger, Norway
City Clinical Hospital n a S P Botkin
🇷🇺Moscow, Russian Federation
St Olavs Hospital
🇳🇴Trondheim, Norway
Ospedale Santa Maria Della Misericordia
🇮🇹Udine, Italy
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Madrid, Communidad Delaware, Spain
City Clinical Hospital # 40
🇷🇺Moscow, Russian Federation
Haukeland Universitetssykehus
🇳🇴Bergen, Norway
Moscow Clinical Scientific Center
🇷🇺Moscow, Russian Federation
GenesisCare Oxford
🇬🇧Oxford, Oxfordshire, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, Kent, United Kingdom
Erciyes Universitesi Tip Fakultesi Hastanesi
🇹🇷Kayseri, Turkey
Helsingborg Lasarett
🇸🇪Helsingborg, Skane Lan, Sweden
Gazi University Medical Faculty Gazi Hospital
🇹🇷Ankara, Turkey
Norrlands Universitetssjukhus
🇸🇪Umea, Sweden
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Singleton Hospital
🇬🇧Swansea, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, Cornwall, United Kingdom
Ankara University Medical Faculty Cebeci Hospital
🇹🇷Ankara, Turkey
Dokuz Eylul University Medical Faculty
🇹🇷Izmir, Turkey
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Centre Hospitalier de Perigueux
🇫🇷Perigueux, France
Centre Hospitalier (CH) William Morey
🇫🇷Chalon sur Saone, France
CHRU de Poitiers La Miletrie
🇫🇷Poitiers, France
Fakultni nemocnice Plzen
🇨🇿Plzen Lochotin, Czechia
Centre Jean Bernard Clinique Victor Hugo
🇫🇷Le Mans cedex 2, France
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
St Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
Icon Cancer Care South Brisbane
🇦🇺South Brisbane, Queensland, Australia
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
GasthuisZusters Antwerpen
🇧🇪Wilrijk, Antwerpen, Belgium
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha, Praha, Hlavni Mesto, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Kralovehradeck Kraj, Czechia
University Hospital Olomouc
🇨🇿Olomouc, Olomouck Kraj, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Prague, Praha, Hlavni Mesto, Czechia
Regionshospitalet Holstebro
🇩🇰Holstebro, Denmark
CHRU Dijon Complexe Du Bocage
🇫🇷Dijon, Cote-d'Or, France
Centre Hospitalier Le Mans
🇫🇷Le Mans, Sarthe, France
Hospital d Instructions des Armees Percy
🇫🇷Clamart, France
Centre Hospitalier de Dunkerque
🇫🇷Dunkerque, France
Centre Hospitalier Regional d'Orleans
🇫🇷Orleans, France
Uberortliche Gemeinschaftspraxis Pasing und Furstenfeldbruck
🇩🇪Munchen, Bayern, Germany
Centre Henri Becquerel
🇫🇷Rouen, France
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Universitatsklinikum Dusseldorf
🇩🇪Dusseldorf, Germany
CHRU Rennes
🇫🇷Rennes Cedex 9, France
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Ospedale Infermi di Rimini
🇮🇹Rimini, Emilia-Romagna, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Emilia-Romagna, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
🇮🇹Pesaro, Marche, Italy
Fondazione del Piemonte per lOncologia (IRCCS)
🇮🇹Candiolo, Piemonte, Italy
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
Azienda Ospedaliero Universitaria Di Modena Policlinico
🇮🇹Modena, Italy
Zuyderland Medisch Centrum
🇳🇱Sittard, Netherlands
Forde Sentralsjukehus
🇳🇴Forde, Norway
Albert Schweitzer Ziekenhuis
🇳🇱Dordrecht, Zuid-Holland, Netherlands
Samara State Medical University
🇷🇺Samara, Russian Federation
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
🇹🇷Ankara, Turkey
Oslo Universitetssykehus HF Rikshospitalet
🇳🇴Oslo, Oppland, Norway
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, Staffordshire, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, Dorset, United Kingdom
Centre Antoine Lacassagne Centre Regional de Lutte Contre Le Cancer
🇫🇷Nice, Alpes-Maritimes, France
University of Maryland
🇺🇸Baltimore, Maryland, United States
Michigan State University
🇺🇸Lansing, Michigan, United States
Lynn Cancer Institute
🇺🇸Boca Raton, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia