Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)

Phase 3

Completed

Conditions: B-Cell Chronic Lymphocytic Leukemia

Interventions: Drug: Lenalidomide
Drug: Chlorambucil

Registration Number: NCT00910910

Lead Sponsor: Celgene

Brief Summary: The purpose of this study is to determine the safety and efficacy of lenalidomide as a first line therapy in treating patients with B-cell Chronic Lymphocytic Leukemia. This study will compare the effects (good and bad) of lenalidomide with chlorambucil.

Detailed Description: After notification from the US Food and Drug Administration (FDA) on 12 July 2013, Celgene agreed to discontinue the lenalidomide treatment for all patients due to an imbalance in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil. No specific causality for this imbalance has been identified to date. Investigators were instructed to immediately discontinue all participants from experimental lenalidomide treatment and inform their patients accordingly. Participants on the Chlorambucil arm may continue up to 12 months (13 cycles) with the last participant completing in March 2014. All randomized participants will continue to be followed for overall survival and secondary primary malignancies.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 450

Inclusion Criteria

Must sign an informed consent form.
Age ≥ 65 years
Must be able to adhere to the study visit schedule and other protocol requirements.
Must have a documented diagnosis of B-cell CLL.
Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
Must agree to follow pregnancy precautions as required by the protocol.
Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
Must agree not to donate blood or semen as defined by the protocol

Exclusion Criteria

Prior treatment for B-cell CLL.
Any medical condition, that would prevent the subject from signing the informed consent form.
Active infections requiring systemic antibiotics.
Systemic infection that has not resolved > 2 months prior to initiating lenalidomide
Pregnant or lactating females.
Participation in any clinical study or having taken any investigational therapy within 28 days.
Known presence of alcohol and/or drug abuse.
Central nervous system (CNS) involvement.
Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ≥3 years. Exceptions include the following:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
History of renal failure requiring dialysis.
Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
Prior therapy with lenalidomide.
Evidence of TLS at screening
Presence of specific hematology and/or chemistry abnormalities
Uncontrolled hyperthyroidism or hypothyroidism
Venous thromboembolism within one year
≥ Grade-2 neuropathy
Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1 - Lenalidomide	Lenalidomide	1 - Lenalidomide
2- Chlorambucil	Chlorambucil	2- Chlorambucil

Primary Outcome Measures

Name	Time	Method
Kaplan-Meier Estimate of Progression Free Survival (PFS)	From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months	Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression
Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014	From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months	Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. Progressive disease included lymphadenopathy, an appearance of any new lesion such as enlarged lymph nodes (\> 1.5 cm), splenomegaly, hepatomegaly or other organ infiltrates, an increase by 50% or more in greatest determined diameter of any previous site or an increase by 50% or more in the sum of the product of diameters of multiple nodes. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014	From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil	AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines	Up to data cut-off date of 18 Feb 2013; approximately 39 months	A best overall response rate is a CR, CRi, nPR or PR and is defined as: Complete Remission (CR): * No lymphadenopathy * No hepatomegaly or splenomegaly * Absence of constitutional symptoms * Polymorphonuclear leukocytes ≥ 1500/ul * No circulating clonal B-lymphocytes * Platelets \> 100,000/ul * Hemoglobin \> 11.0 g/dl * Normocellular \<30% lymphocytes, no B-lymphoid nodules; Incomplete Clinical Response (CRi): • CR without bone marrow biopsy confirmation. Nodular Partial Response (nPR): • CR with the presence of residual clonal nodules. Partial Response (PR) requires: * ≥ 50% decrease in peripheral blood lymphocyte count * ≥ 50% reduction in lymphadenopathy * ≥ 50% reduction in size of liver and/or spleen * 1 or more of the following: * Polymorphonuclear leukocytes ≥ 1500/ul * Platelets \>100,000/ul
Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014	Up to data cut-off of 31 March 2014; approximately 53 months	A best overall response rate is a CR, CRi, nPR or PR and is defined as: Complete Remission (CR): * No lymphadenopathy * No hepatomegaly or splenomegaly * Absence of constitutional symptoms * Polymorphonuclear leukocytes ≥ 1500/ul * No circulating clonal B-lymphocytes * Platelets \> 100,000/ul * Hemoglobin \> 11.0 g/dl * Normocellular \<30% lymphocytes, no B-lymphoid nodules; Incomplete Clinical Response (CRi): • CR without bone marrow biopsy confirmation. Nodular Partial Response: • CR with the presence of residual clonal nodules. Partial Response requires: * ≥ 50% decrease in peripheral blood lymphocyte count * ≥ 50% reduction in lymphadenopathy * ≥ 50% reduction in size of liver and/or spleen * 1 or more of the following: * Polymorphonuclear leukocytes ≥ 1500/ul * Platelets \>100,000/ul
Time to Response for a Later Cut-off Date of 31 March 2014	Up to data cut-off of 31 March 2014; up to approximately 53 months	Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines
Kaplan Meier Estimate for Overall Survival at the Final Analysis	Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months	Overall Survival is defined as the time between randomization and death from any cause. Overall survival was censored at the last date that the subject was known to be alive for participants who were alive as of the data cutoff date and for participants who were lost to follow-up before death was documented.
Number of Participants With Adverse Events (AEs)	From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil	AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Time to Response	Up to data cut-off of 18 Feb 2013; up to approximately 39 months	Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines
Kaplan Meier Estimate of Overall Survival	Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months	Overall Survival is defined as the time between randomization and death from any cause.
Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014	Up to data cut-off of 31 March 2014; up to approximately 53 months	Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) patients who had not progressed at the time of analysis; 2) patients who had withdrawn consent or were lost to follow-up prior to documentation of progression
Kaplan-Meier Estimate for Duration of Response	Up to data cut-off of 18 Feb 2013; up to approximately 39 months	Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had withdrawn consent or were lost to follow-up prior to documentation of progression
Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment	Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months	Subsequent anti-cancer therapies administered to participants following the discontinuation of study drug (either Lenalidomide or Chlorambucil)
Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument	Day 1 and once every 8 weeks	The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease. The FACT-Leu is described as including 27 items that assess 17 physical symptoms (fevers, bleeding, general pain, stomach pain, chills, night sweats, bruising, lymph node swelling, weakness, tiredness, weight loss, appetite, shortness of breath, functional ability, diarrhea, concentration, and mouth sores) and 10 emotional/social concerns (frustration with activity limitation, discouraged by illness, future planning, uncertainty, worry about illness, emotional lability, isolation, infertility concern, family worry, and worry about infections).
Euro Quality of Life Five Dimension (EQ-5D) Questionnaire	Day 1 and once every 8 weeks	The standardized extended version of EQ-5D was designed for the collection of health state values using a visual analogue scale (VAS) rating scale - a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.

Trial Locations

Locations (165): Drexel University, College of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Hopital de Jolimont
🇧🇪
Haine-Saint Paul, Belgium
CHU Mont -Godinne
🇧🇪
Yvoir, Belgium
BIOCANCER - Centro de Pesquisa e Tratamento do Câncer S/A
🇧🇷
Belo Horizonte, Minas Gerais, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Shaare Zedek Medical Center
🇮🇱
Jerusalem, Israel
New York Medical College
🇺🇸
Valhalla, New York, United States
Spitalul Clinic Municipal de Urgenta Timisoara
🇷🇴
Timisoara, Romania
Spitalul Clinic Judetean de Urgenta Sf Spiridon Iasi
🇷🇴
Iasi, Romania
Sheba Medical Center
🇮🇱
Tel Hashomer, Israel
Fundacao Pio XII - Hospital de Cancer de Barretos
🇧🇷
Barretos, São Paulo, Brazil
Hospitais da Universidade de Coimbra
🇵🇹
Coimbra, Portugal
Institutul Clinic Fundeni
🇷🇴
Bucharest, Romania
North Shore University Hospital
🇳🇿
Takapuna, New Zealand
General Hospital, Eastern Health
🇨🇦
St John's, Newfoundland and Labrador, Canada
Medical University of Vienna Internalmedicine 1, Hematology
🇦🇹
Vienna, Austria
Instituto Portugues Oncologia do Porto Francisco Gentil EPE
🇵🇹
Porto, Portugal
Innovative Clinical Research Institute
🇺🇸
Whittier, California, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
California Cancer Associates for Research and Excellence cCARE
🇺🇸
Escondido, California, United States
Central Texas Veterans Health Care System
🇺🇸
Temple, Texas, United States
Universitaetsklinik Innsbruck
🇦🇹
Innsbruck, Austria
Monte Tabor - Hospital Sao Rafael
🇧🇷
Salvador, Bahia, Brazil
Hospital Erasto Gaertner
🇧🇷
Curitiba, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Instituto Oncologico
🇨🇱
Renaca, Chile
Rabin Medical Center
🇮🇱
Petach Tikva, Israel
Klinika Chorob wewnetrznych i Hematologii
🇵🇱
Warszawa, Poland
Spaame Ziekenhuis
🇳🇱
Hoofddorp, Netherlands
Clinical Center Kragujevac
🇷🇸
Kragujevac, Serbia
Clinical Center Nis
🇷🇸
Nis, Serbia
NUZ Central Clinical Hospital
🇷🇺
Moscow, Russian Federation
Narodny onkologicky ustav
🇸🇰
Bratislava, Slovakia
University Witwatersrand Oncology
🇿🇦
Parktown, South Africa
Royal Bournemouth General Hospital
🇬🇧
Bournemouth, United Kingdom
Hospital Universitario Marques de Valdecilla
🇪🇸
Santander, Spain
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Nevada Cancer Research Foundation
🇺🇸
Las Vegas, Nevada, United States
Roskilde University Hospital
🇩🇰
Roskilde, Denmark
Azienda Ospedaliero Universitaria di Modena
🇮🇹
Modena, Italy
Ospedale S. Chiara
🇮🇹
Pisa, Italy
St George's Healthcare NHS Trust
🇬🇧
London, United Kingdom
Roswell Park Cancer Center
🇺🇸
Buffalo, New York, United States
University Hematology Oncology Inc.
🇺🇸
Centralia, Illinois, United States
North Chicago VA Medical Center
🇺🇸
North Chicago, Illinois, United States
Cancer Center of Central Connecticut
🇺🇸
Southington, Connecticut, United States
Medical Consultants, PC
🇺🇸
Muncie, Indiana, United States
Floyd Memorial Cancer Center of Indiana, a division of Floyd Memorial Hospital and Health Services
🇺🇸
New Albany, Indiana, United States
Saint Louis University Cancer Center
🇺🇸
Saint Louis, Missouri, United States
Purchase Cancer Group
🇺🇸
Paducah, Kentucky, United States
Oncology and Hematology Associates, PA
🇺🇸
Denville, New Jersey, United States
The Cancer Center, Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Pottstown Memorial Medical Center
🇺🇸
Pottstown, Pennsylvania, United States
Somerset Hematology-Oncology Associates
🇺🇸
Somerville, New Jersey, United States
Gabrail Cancer Center Research
🇺🇸
Canton, Ohio, United States
Swedish Tumor Institute
🇺🇸
Seattle, Washington, United States
South Carolina Cancer Specialists
🇺🇸
Hilton Head Island, South Carolina, United States
Geisinger Health System
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Berks Hematology-Oncology Associates
🇺🇸
West Reading, Pennsylvania, United States
Providence St. Mary Regional Cancer Center
🇺🇸
Walla Walla, Washington, United States
Princess Alexandra Hospital
🇦🇺
Woolloongabba, Queensland, Australia
Royal Melbourne Hospital
🇦🇺
Melbourne, Victoria, Australia
IMVS
🇦🇺
Adelaide, South Australia, Australia
Flinders Medical Centre
🇦🇺
Bedford Park, Australia
Western Hospital
🇦🇺
Footscray, Victoria, Australia
Nepean Hospital
🇦🇺
Kingswood, NSW, Australia
St. Vincent Hospital
🇦🇺
Fitzroy, Australia
Calvary Mater Hospital
🇦🇺
Waratah, Australia
AZ Groeninge
🇧🇪
Kortrijk, Belgium
Westmead Hospital Australia
🇦🇺
Westmead, Australia
Institut Jules Bordet
🇧🇪
Brussels, Belgium
Hopital Erasme
🇧🇪
Brussels, Belgium
UZ Leuven
🇧🇪
Leuven, Belgium
Hospital Universitario de Brasilia
🇧🇷
Brasílía, Brazil
Hospital Israelita Albert Einstein
🇧🇷
Morumbi, Brazil
Pro Onco Centro de Tratamento Oncologico
🇧🇷
Londrina, Brazil
Instituto Estadual Arthur de Siqueira Cavalcanti - HEMORIO
🇧🇷
Rio de Janeiro, Brazil
Instituto Nacional de Cancer - INCA
🇧🇷
Rio de Janeiro, Brazil
University hospital Sveti Georgi Hematology Clinic
🇧🇬
Plovdiv, Bulgaria
MHAT Georgi Stranski PlevenHematology Clinic
🇧🇬
Pleven, Bulgaria
Instituto de Ensino e Pesquisa Sao Lucas
🇧🇷
São Paulo, Brazil
Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
🇧🇷
Santo Andre, Brazil
Fundação Antonio Prudente - AC Camargo Câncer center
🇧🇷
São Paulo, Brazil
University hospital Sveta Marina
🇧🇬
Varna, Bulgaria
Hospital Charles LeMoyne
🇨🇦
Greenfield Park, Quebec, Canada
National Specialized Hospital for Active Treatment of Hematology Diseases
🇧🇬
Sofia, Bulgaria
Military Medical Academy
🇧🇬
Sofia, Bulgaria
Sacre-Couer Hospital
🇨🇦
Montreal, Quebec, Canada
Instituto Clinico Oncologico del Sur ICOS
🇨🇱
Temuco, Chile
Oncomedica S.A.
🇨🇴
Monteria, Colombia
University Hospital Centre Split
🇭🇷
Split, Croatia
Klinicka bolnica Dubrava Klinika za unutarnje bolesti Odjel za Hematologiju
🇭🇷
Zagreb, Croatia
Fakultni nemocnice Ostrava
🇨🇿
Ostrava, Czechia
General Hospital Sveti Duh
🇭🇷
Zagreb, Croatia
Faculty Hospital Kralovske Vinohrady
🇨🇿
Prague, Czechia
University Hospital2.Dep.Intern.Med. Hematology
🇨🇿
Hradec Kralove, Czechia
Rigshospitalet University Hospital
🇩🇰
Copenhagen, Denmark
Herlev University Hospital Dep of hematology
🇩🇰
Harlev, Denmark
Bergonie Institut
🇫🇷
Bordeaux, France
CHU Hautepierre
🇫🇷
Strasbourg, France
Polyclinique Bordeaux Nord Aquitaine
🇫🇷
Bordeaux, France
CHU Dupuytren
🇫🇷
Limoges, France
Hopital de l'Archet 1
🇫🇷
Nice, France
Kaposi Mor Oktato Korhaz
🇭🇺
Kaposvar, Hungary
CHRU
🇫🇷
Grenoble cedex 09, France
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
🇭🇺
Debrecen, Hungary
Komarom-Esztergom Megye Onkormanyzat Szent Borbala Korhaza
🇭🇺
Tatabanya, Hungary
Szegedi TudomanyegyetemII Belgyogyaszati Klinika
🇭🇺
Szeged, Hungary
Petz Aladar Country Hospital
🇭🇺
Vasvari Pal U. 2, Hungary
Ha'Emek Medical Center
🇮🇱
Afula, Israel
Barzilai Medical Center
🇮🇱
Ashkelon, Israel
Soroka University Medical Center
🇮🇱
Beer Sheva, Israel
Bnei Zion Medical Center
🇮🇱
Haifa, Israel
Meir Medical Center
🇮🇱
Kfar-Saba, Israel
Western Galilee Hospital
🇮🇱
Naharia, Israel
Kaplan Medical Center
🇮🇱
Rehovot, Israel
Tel Aviv Sourasky Medical Center Department of Hematology
🇮🇱
Tel Aviv, Israel
Azienda Ospedaliera Universitaria Careggi
🇮🇹
Firenze, Italy
IRCSS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
🇮🇹
Milan, Italy
Azienda Ospedaliera Policlinico di Bari
🇮🇹
Bari, Italy
Ospedale San Raffaele S.r.l.
🇮🇹
Milan, Italy
Istituto Europeo di Oncologia - IEO
🇮🇹
Milan, Italy
Ospedale Cardarelli
🇮🇹
Naples, Italy
Universita del Piemonte Orientale
🇮🇹
Novara, Italy
Universita degli Studi di Padova
🇮🇹
Padova, Italy
AOU San Luigi Gonzaga
🇮🇹
Orbassano, Italy
Azienda Ospedaliera Ospedale San Carlo
🇮🇹
Potenza, Italy
Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
🇮🇹
Siena, Italy
Isala Klinieken
🇳🇱
Zwolle, Netherlands
Maxima Medisch Centrum
🇳🇱
Eindhoven, Netherlands
Ospedale Umberto I
🇮🇹
Torrette Di Ancona, Italy
Christchurch Hospital
🇳🇿
Christchurch, New Zealand
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika
🇵🇱
Lodz, Poland
Specjalistyczny Szpital miejski im. Kopernika
🇵🇱
Torun, Poland
Nowotworww Krwi i Transplantacji Szpiku
🇵🇱
Wroclaw, Poland
Spitalul Clinic Coltea
🇷🇴
Bucharest, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
🇷🇴
Sibiu, Romania
Archangelsk Regional Clinical Hospital
🇷🇺
Arkhangelsk, Russian Federation
City Hospital 8
🇷🇺
Barnaul, Russian Federation
Russian Academy of Medical Sciences Institution
🇷🇺
Moscow, Russian Federation
Regional Clinical Hospital 1
🇷🇺
Ekaterinburg, Russian Federation
St. Petersburg Research Institute of Hematology and Blood Transfusion
🇷🇺
St. Petersburg, Russian Federation
GUZ Nizhegorodskaya Regional Clinical Hospital
🇷🇺
Nizhniy Novgorod, Russian Federation
MUZ City clinical hospital
🇷🇺
Novosibirsk, Russian Federation
Moscow GUZ City Clinical Hospital
🇷🇺
Moscow, Russian Federation
GUS Leningrad Regional Clinical Hospital
🇷🇺
St. Petersburg, Russian Federation
Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov
🇷🇺
St. Petersburg, Russian Federation
Pretoria Academic Hospital
🇿🇦
Pretoria, South Africa
Hospital Universitario de la Princesa
🇪🇸
Madrid, Spain
Hospital Universitario Vall D hebron
🇪🇸
Barcelona, Spain
Martinska Fakultna Nemocnica
🇸🇰
Martin, Slovakia
Mary Potter Oncology Centre
🇿🇦
Pretoria, South Africa
Hospital Germans Trias I Pujol
🇪🇸
Badalona, Spain
Hospital Ramon y Cajal
🇪🇸
Madrid, Spain
Hospital Universitario Puerta de Hierro-Majadahonda
🇪🇸
Majadahonda, Spain
Hospital General Universitario Morales Messeguer
🇪🇸
Murcia, Spain
Hospital Universitario de Salamanca
🇪🇸
Salamanca, Spain
Hospital Donostia
🇪🇸
San Sebastian, Spain
Hospital Universitario La Fe
🇪🇸
Valencia, Spain
St. Bartholomew's and The Royal London Hospital
🇬🇧
London, United Kingdom
Columbia St Marys Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States
Regional Health Authority B-Saint John Regional Hospital
🇨🇦
Saint John, New Brunswick, Canada
University Hospital Centre Zagreb
🇭🇷
Zagreb, Croatia
Charleston Hematology Oncology P.A.
🇺🇸
Charleston, South Carolina, United States