A Study Evaluating the Safety and Efficacy of Venetoclax (GDC-0199) Plus Bendamustine + Rituximab (BR) in Comparison With BR or Venetoclax Plus Rituximab in Participants With Relapsed and Refractory Follicular Non-Hodgkin's Lymphoma (fNHL)
- Conditions
- Follicular Lymphoma
- Interventions
- Registration Number
- NCT02187861
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This open-label, international, multicenter study will investigate the safety and efficacy of venetoclax (GDC-0199) in combination with bendamustine plus rituximab (venetoclax + BR) compared with BR alone in participants with relapsed and refractory fNHL, comparing two chemotherapy-containing regimens (Chemotherapy-Containing Cohort). In addition, an exploratory analysis of the safety and efficacy of venetoclax in combination with rituximab (venetoclax + rituximab), a chemotherapy-free regimen, will be performed (Chemotherapy-Free Cohort). Assignment to the Chemotherapy-Containing or Chemotherapy-Free Cohort will be decided at the discretion of the Investigator, unless one of the cohorts is not open to enrollment; in which case, participants may be enrolled only to the open cohort. The first 6 participants enrolled in the Chemotherapy-Containing Cohort (or more if required) will comprise the Safety Run-In group for Treatment Arm B, dosing venetoclax at 600 milligrams (mg) in combination with BR. Once a dose has been chosen from the Safety Run-In Period, randomization to the two treatment arms of the Chemotherapy-Containing Cohort (Arms B and C) will begin.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 163
- Participants must have histologically confirmed follicular lymphoma (FL) of Grade 1, 2, or 3a
- Participants must have received at least one prior therapy for FL
- For participants potentially receiving chemotherapy: if the participant has received prior bendamustine, response duration must have been greater than (>) 1 year
- At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Adequate hematologic function
- For female participants of childbearing potential and male participants with female partners of childbearing potential, agreement to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception throughout the course of study treatment and for at least 30 days after the last dose of venetoclax and 12 months after the last dose of rituximab, whichever is longer
- Confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined specifications prior to study enrollment
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- Contraindication to potential treatment agents
- Ongoing corticosteroid use >30 milligrams per day (mg/day) of prednisone or equivalent. Participants receiving corticosteroid treatment with less than equal to (</=) 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks duration prior to randomization (Cycle 1 Day 1)
- Primary central nervous system (CNS) lymphoma
- Vaccination with live vaccines within 28 days prior to treatment
- Chemotherapy or other investigational therapy within five half-lives of a biologic agent with a minimum of 28 days prior to the start of Cycle 1
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the participant
- Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day 1
- Requires the use of warfarin
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Presence of positive test results for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
- Participants who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation
- Participants with occult or prior hepatitis B virus (HBV) infection may be included if HBV deoxyribonucleic acid (DNA) is undetectable at screening. These participants must be willing to undergo monthly HBV DNA test until at least 12 months after the last treatment cycle
- Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)
- Pregnant or lactating
- Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1), other than for diagnosis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy-Containing Cohort: Arm C (BR) Bendamustine Participants will receive rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles. Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Venetoclax Participants will receive venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in will continue until first 9 participants complete the safety observation window of 28 days. Participants will continue receiving the same treatment as decided for Arm B. Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Bendamustine Participants will receive venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in will continue until first 9 participants complete the safety observation window of 28 days. Participants will continue receiving the same treatment as decided for Arm B. Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Rituximab Participants will receive venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in will continue until first 9 participants complete the safety observation window of 28 days. Participants will continue receiving the same treatment as decided for Arm B. Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Rituximab Participants will receive venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle will be of 28 days. Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Venetoclax Participants will receive venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle will be of 28 days. Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) Venetoclax Participants will receive venetoclax at doses decided from safety run-in orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles. Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) Bendamustine Participants will receive venetoclax at doses decided from safety run-in orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles. Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) Rituximab Participants will receive venetoclax at doses decided from safety run-in orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles. Chemotherapy-Containing Cohort: Arm C (BR) Rituximab Participants will receive rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as Per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA) 6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days) CMR: a score 1 (no uptake above background), 2 (uptake less than or equal to \[\<=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \<=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites with no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With CMR According to IRC as Per Lugano Classification, Using PET Scan at Year 1 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (uptake \<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at PRA 4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days) CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at Year 1 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) CR: defined as reduction of longest transverse diameter of lesion (LDi) of target nodes/nodal masses to \<=1.5 centimeters (cm), and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) CR: defined as reduction of LDi of target nodes/nodal masses to \<=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) OR was defined as CMR or PMR. CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PMR: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) OR was defined as CMR or Partial Metabolic Response (PMR). CMR: a score 1 (no uptake above background), 2 (uptake \<=mediastinum), or 3 (\<mediastinum but \<=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PMR: a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) OR was defined as CR or Partial Response (PR). CR: reduction of LDi of target nodes/nodal masses to \<=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: greater than or equal to (\>=) 50 percent (%) decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least \>50% beyond normal; and no new lesions. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Apparent Clearance (CL) of Venetoclax Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days) CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Apparent Volume of Distribution (Vd) of Venetoclax Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days) Vd was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time to Maximum Plasma Concentration (Tmax) of Venetoclax Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days) Maximum Plasma Concentration (Cmax) of Venetoclax Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days) Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days) OR was defined as CR or PR. CR: reduction of LDi of target nodes/nodal masses to \<=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: \>=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least \>50% beyond normal; and no new lesions. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET or CT Scan Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years) OR was defined as CMR/CR or PMR/PR. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing).
Duration of Response (DOR) According to Investigator as Per Lugano Classification, Using PET or CT Scan From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years) DOR was defined as time from CMR/CR or PMR/PR until progressive disease (PD) or death due to any cause. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing). DOR was calculated using Kaplan-Meier method.
Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan) or Death Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years) PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan.
Percentage of Participants Who Died Due to Any Cause Baseline until death due to any cause (assessed up to approximately 2.5 years Progression-Free Survival (PFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years) PFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) until the date of disease progression, or death due to any cause. PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. PFS was calculated using Kaplan-Meier method.
Overall Survival (OS) Baseline until death due to any cause (assessed up to approximately 2.5 years) OS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to death due to any cause. For participants who are alive, OS was censored at the last contact. OS was calculated using Kaplan-Meier method.
Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years) PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan.
Event-Free Survival (EFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years) EFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to the date of disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first. PD: a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. EFS was calculated using Kaplan-Meier method.
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Concentration (AUClast) of Venetoclax Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days) Area under the plasma concentration versus time curve from zero to the last measured concentration (AUClast).
Area Under the Plasma Concentration-Time Curve From Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days) Area under the plasma concentration versus time curve from time 0 (pre-dose) to 8 hours post dose (AUC0-8h).
Trial Locations
- Locations (71)
Royal Prince Alfred Hospital; Medical Oncology
🇦🇺Camperdown, New South Wales, Australia
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
British Columbia Cancer Agency
🇨🇦Kelowna, British Columbia, Canada
Saskatoon Cancer Centre; Uni of Saskatoon Campus
🇨🇦Saskatoon, Saskatchewan, Canada
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago College of Medicine
🇺🇸Chicago, Illinois, United States
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Sidney Kimmel Comp Cancer Ctr
🇺🇸Baltimore, Maryland, United States
Azienda Ospedale San Giovanni
🇮🇹Torino, Piemonte, Italy
Institut de Cancerologie de l'Ouest
🇫🇷Angers, France
West Virginia Uni Med. Center - Robert Byrd Health Science
🇺🇸Morgantown, West Virginia, United States
Westmead Hospital; Haematology
🇦🇺Sydney, New South Wales, Australia
Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik
🇩🇪Mainz, Germany
Universitätsklinikum Jena; Klinik für Innere Medizin II
🇩🇪Jena, Germany
Centre Jean Bernard
🇫🇷Le Mans, France
CHU Montpellier
🇫🇷Montpellier, France
St James University Hospital
🇬🇧Leeds, United Kingdom
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
🇮🇹Bologna, Emilia-Romagna, Italy
Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie
🇩🇪Lübeck, Germany
Centre Hospitalier Lyon Sud; Hematolgie
🇫🇷Pierre Benite, France
Ospedale Niguarda Milano
🇮🇹Milano, Lombardia, Italy
Az. Osp. Di Careggi; Divisione Di Ematologia
🇮🇹Firenze, Toscana, Italy
Townsville General Hospital
🇦🇺Douglas, Queensland, Australia
Städtisches Klinikum Dessau
🇩🇪Dessau-Roßlau, Germany
Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
🇩🇪Essen, Germany
Queen Elizabeth Hospital; Haematology
🇦🇺Woodville South, South Australia, Australia
Universitätsklinikum Ulm; Apotheke
🇩🇪Ulm, Germany
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
🇮🇹Meldola, Emilia-Romagna, Italy
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
🇨🇦Toronto, Ontario, Canada
AZ Sint Jan
🇧🇪Brugge, Belgium
Irccs Policlinico San Matteo; Divisione Di Ematologia
🇮🇹Pavia, Lombardia, Italy
Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie
🇩🇪Würzburg, Germany
Ospedale Infermi di Rimini
🇮🇹Rimini, Emilia-Romagna, Italy
Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III
🇩🇪Chemnitz, Germany
Hopital Maisonneuve- Rosemont; Oncology
🇨🇦Montreal, Quebec, Canada
CHU Clermont Ferrand - Hôpital d'Estaing
🇫🇷Clermont Ferrand cedex 1, France
Hopital Henri Mondor
🇫🇷Creteil, France
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Leicester Royal Infirmary; Dept. of Medical Oncology
🇬🇧Leicester, United Kingdom
Royal Marsden Nhs Trust; Consultant Cancer Physician
🇬🇧London, United Kingdom
Christie Hospital; Breast Cancer Research Office
🇬🇧Manchester, United Kingdom
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
University of Kansas; Medical Center & Medical pavilion
🇺🇸Westwood, Kansas, United States
St George Hospital
🇦🇺Kogarah, New South Wales, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Southern Cancer Center, PC
🇺🇸Mobile, Alabama, United States
UCLA School of Medicine; Hematology/Oncology
🇺🇸Los Angeles, California, United States
Primary Healthcare Associates SC - Harvey
🇺🇸Harvey, Illinois, United States
Nothwest Georgia Oncology Centers P.C
🇺🇸Austell, Georgia, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
James P. Wilmot Cancer Center
🇺🇸Rochester, New York, United States
University of Pennsylvania; School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Chum Hopital Notre Dame; Centre D'Oncologie
🇨🇦Montreal, Quebec, Canada
CHU de Dijon - Hopital le Bocage
🇫🇷Dijon, France
Universitätsklinikum Köln; Klinik I für Innere Medizin
🇩🇪Koeln, Germany
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
🇩🇪Dresden, Germany
Ospedale di Ravenna
🇮🇹Ravenna, Emilia-Romagna, Italy
Asst Papa Giovanni XXIII
🇮🇹Bergamo, Lombardia, Italy
University College London, Department of Haematology
🇬🇧London, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Churchill Hospital; Oxford Cancer and Haematology Centre
🇬🇧Oxford, United Kingdom
VCU Massey Cancer Center
🇺🇸Richmond, Virginia, United States