Selinexor Treatment of Refractory Myeloma
- Registration Number
- NCT02336815
- Lead Sponsor
- Karyopharm Therapeutics Inc
- Brief Summary
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd) dosed twice weekly in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or quad refractory MM (Part 1 only).
- Detailed Description
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd), both dosed twice weekly in each four-week cycle, in patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and daratumumab.
This study consists of two parts:
* Part 1 enrolled patients with both quad-refractory MM and penta-refractory MM.
* Part 2 will enroll patients with penta-refractory MM only.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 202
Measurable MM based on modified IMWG guidelines. Defined by at least one of the following:
-
Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA
-
Urinary M-protein excretion ≥ 200 mg/24 hours
-
Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal
-
If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidimetry are acceptable
- Must have previously received ≥ 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met.
- MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
- Active smoldering MM.
- Active plasma cell leukemia.
- Documented systemic amyloid light chain amyloidosis.
- Active CNS MM.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Selinexor Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory multiple myeloma (MM) (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) Selinexor 80 milligrams (mg) plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) Selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). Part 1 Dexamethasone Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory multiple myeloma (MM) (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) Selinexor 80 milligrams (mg) plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) Selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). Part 2 Selinexor Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, Selinexor 80 mg post oral (PO) plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). Part 2 Dexamethasone Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, Selinexor 80 mg post oral (PO) plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months).
- Primary Outcome Measures
Name Time Method Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC) Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months) IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (\>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to lesser than (\<) 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and lesser than or equal to (\<=) 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells in bone marrow biopsy by immunohistochemistry).
- Secondary Outcome Measures
Name Time Method Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months) IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire Baseline, Day 1 of Cycle 2 to Cycle 20 (up to a maximum of 17 months) FACT-MM combines the general version of the FACT (FACT-G) with a MM-specific sub-scale (14 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI); total of 41 items) is the primary measurement of interest, comprised of the Physical and Functional sub-scales plus the MM-specific sub-scale. Each item is rated on a 5-point Likert scale, ranging from 0 ("Not at all") to 4 ("Very much"), therefore the TOI has a score ranging from 0 to 120. Higher scores indicated improvement in well being.
Volume of Distribution (V/F) of Selinexor in Plasma Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose Vz/F of selinexor in plasma was reported.
Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months) IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months) IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>= 5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC Baseline up to a maximum of 17 months IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).
Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months) IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Part 2: Disease Control Rate (DCR) Every 12 weeks until progressive disease or death due to any cause, up to 17 months DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: CR as defined+Normal FLC ratio+Absence of clonal cells by immunohistochemistry).
Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent events are events between first dose of study drug and up to last dose of study treatment + 30 days (inclusive) that were absent before treatment or that worsened relative to pre-treatment state.
Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months) IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Part 2: Overall Survival (OS) From start of study treatment to death (maximum duration of 17 months) OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method.
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.
Part 2: Time to Next Treatment (TTNT) From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 17 months) TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.
Apparent Clearance (CL/F) of Selinexor in Plasma Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose CL/F of selinexor in plasma was reported.
Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC Baseline up to a maximum of 13 months IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).
Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months) IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Part 1: Overall Survival (OS) From start of study treatment to death (maximum duration of 13 months) OS was defined as the duration (in months) from start of study treatment to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. Analysis was performed using Kaplan-Meier method.
Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months) IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months) IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Part 1: Time to Next Treatment (TTNT) From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 13 months) TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.
Trial Locations
- Locations (61)
Jonnsson Comprehensive Cancer Center / University of Los Angeles
🇺🇸Los Angeles, California, United States
Hackensack University Medical Center / John Therurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Sylvester, University of Miami
🇺🇸Miami, Florida, United States
University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
Indiana University Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Mayo Clinic (AZ)
🇺🇸Scottsdale, Arizona, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University Hospital Krems, Department of Internal Medicine II
🇦🇹Krems, Austria
Kaiser Permanente Northwest OR
🇺🇸Portland, Oregon, United States
University Hospital Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
City of Hope
🇺🇸Duarte, California, United States
Emory University / Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Johns Hopkins Medicine
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Florida Health Cancer Center- Shands Cancer Center Hospital
🇺🇸Gainesville, Florida, United States
H. Lee Moffitt Cancer Center Research Institute
🇺🇸Tampa, Florida, United States
UNC-Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Mt Sinai NYC
🇺🇸New York, New York, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Valley Hospital
🇺🇸Paramus, New Jersey, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Karmanos Cancer Institute / Wayne State University
🇺🇸Detroit, Michigan, United States
Vanderbilt University Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
NYU Perlmutter Cancer Center
🇺🇸New York, New York, United States
Claude Huriez Hospital, Department of Blood Diseases
🇫🇷Lille, France
Salzburg Regional Hospital Müllner
🇦🇹Salzburg, Austria
Brabois Adults Hospital
🇫🇷Nancy, France
Hopital Saint-Antoine, Service d´Hematologie Clinique et Therapie Cellulaire
🇫🇷Paris, France
Necker Children's Hospital
🇫🇷Paris, France
ZNA Stuivenberg
🇧🇪Antwerp, Belgium
General Hospital Saint-Jan
🇧🇪Brugge, Belgium
Jules Bordet Institute
🇧🇪Brussels, Belgium
Nantes University Hospital Center
🇫🇷Nantes, France
University Hospital Ghent
🇧🇪Ghent, Belgium
UCL Saint-Luc
🇧🇪Brussels, Belgium
UCL Mont-Godinne
🇧🇪Yvoir, Belgium
La Pitie-Salpetriere University Hospital, Department of Clinical Hematology
🇫🇷Paris, France
University Hospital Freiburg, Department of Internal Medicine I
🇩🇪Freiburg, Germany
Universitätsklinikum Heidelberg Medizinische Klinik V
🇩🇪Heidelberg, Germany
Universitätsmedizin Mainz
🇩🇪Mainz, Germany
University hospital of Tuebingen, Internal Medicine II
🇩🇪Tübingen, Germany
National & Kapodistrain University of Athens School of Medicine, Alexandra Hospital
🇬🇷Athens, Greece
Med. Klinik und Poliklinik II Universitätsklinikum
🇩🇪Würzburg, Germany
Universitätsklinikum des Saarlandes Klinik für Innere Medizin I
🇩🇪Homburg, Germany
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Baylor Sammons Cancer Center
🇺🇸Dallas, Texas, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Kaiser Permanente- Hawaii
🇺🇸Honolulu, Hawaii, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Washington University St. Louis
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Columbia University
🇺🇸New York, New York, United States
Abramson Cancer Center of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Medical University Vienna, Department of Internal Medicine I
🇦🇹Vienna, Austria
South Lyon Hospital Center, Department of Clinical Hematology
🇫🇷Lyon, France
BAG Oncology Gemeinschaftspraxis
🇩🇪Dresden, Germany
Smilow Cancer Hospital
🇺🇸New Haven, Connecticut, United States