A Study of Bevacizumab (Avastin) in Combination With Rituximab (MabThera) and CHOP (Cyclophosphamide, Hydroxydaunorubicin [Doxorubicin], Oncovin [Vincristine], Prednisone) Chemotherapy in Patients With Diffuse Large B-cell Lymphoma

Phase 3

Terminated

• Conditions: B-cell Lymphoma
• Interventions: Drug: Rituximab; Drug: Bevacizumab; Drug: CHOP; Drug: Placebo

• Registration Number: NCT00486759
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This 2-arm study was designed to compare the efficacy and safety of bevacizumab (Avastin) in combination with rituximab (MabThera) and CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) chemotherapy (R-CHOP) versus rituximab plus CHOP chemotherapy (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL). Patients were randomized to receive 8 cycles of treatment with R-CHOP plus bevacizumab or R-CHOP plus placebo. Treatment with bevacizumab/placebo and R-CHOP was given either on a 2-week or 3-week schedule and bevacizumab was given at a weekly average dose of 5 mg/kg (10 mg/kg for 2-week cycles and 15 mg/kg for 3-week cycles).

Detailed Description

An independent Data and Safety Monitoring Board (DSMB) was established to review safety data collected during the study on an ongoing basis. At its meeting in December 2009, the DSMB noted a trend for increased cardiac toxicity in the experimental arm (R-CHOP + bevacizumab) compared with the control arm (R-CHOP + placebo). Additional efficacy analyses of data from 720 randomized patients were presented at a DSMB meeting on May 22, 2010; they indicated no improvement in efficacy with the addition of bevacizumab to R-CHOP. It was noted, however, that there was an apparent increase in the risk of cardiotoxicity, premature treatment withdrawal, serious adverse events (SAEs), fatal adverse events (AEs), and perforation/ulcer in the experimental arm. Based on its assessment of an increased risk with unlikely benefit for patients randomized to the experimental arm, the DSMB recommended that further enrollment in the study be permanently halted and that bevacizumab be discontinued for any patients randomized to the experimental arm. On May 31, 2010, the sponsor took the decision to stop enrollment into the study and the bevacizumab treatment was terminated with immediate effect as recommended by the DSMB.

The study protocol was amended. The primary objective of the study was changed from evaluation of efficacy to evaluation of safety and the study was extended to include an 18-month safety follow-up period. Because enrollment was terminated prematurely resulting in fewer enrolled patients than planned, the outcome measure data are premature due to fewer than expected events.

The time frame for the reporting of serious adverse events was modified. Serious adverse events (SAE) unrelated to study treatment were reported until 1 year post-treatment or until new anti-lymphoma treatment was initiated. SAEs judged to be related to study treatment and congestive heart failure events were reported at any time during the study.

Study Timeline

• Study First Submitted: 2007-06-14
• Study First Submitted QC: 2007-06-14
• Study First Posted: 2007-06-15
• Study Start: 2007-07-26
• Primary Completion: 2011-11-30
• Study Completion: 2011-11-30
• Results First Submitted: 2012-11-28
• Results First Submitted QC: 2012-11-28
• Results First Posted: 2012-12-31
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-26
• Last Update Posted: 2017-07-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 787

Inclusion Criteria

• Adult patients, ≥ 18 and < 80 years of age.
• CD20-positive diffuse large B-cell lymphoma.
• Low-intermediate, high-intermediate, or high risk disease and/or bulky tumor (largest diameter ≥ 7.5 cm).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria

• Prior treatment for diffuse large B-cell lymphoma.
• Types of non-Hodgkin's lymphoma other than diffuse large B-cell lymphoma (DLBCL).
• Central nervous system (CNS) involvement of lymphoma.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + rituximab + CHOP	Placebo	Patients received placebo to bevacizumab on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).
Placebo + rituximab + CHOP	Rituximab	Patients received placebo to bevacizumab on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).
Bevacizumab + rituximab + CHOP	Bevacizumab	Patients received bevacizumab 5 mg/kg/week on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).
Placebo + rituximab + CHOP	CHOP	Patients received placebo to bevacizumab on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).
Bevacizumab + rituximab + CHOP	CHOP	Patients received bevacizumab 5 mg/kg/week on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).
Bevacizumab + rituximab + CHOP	Rituximab	Patients received bevacizumab 5 mg/kg/week on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Baseline to end of the study (up to 4 years, 4 months)	PFS was defined as the time from the date of randomization to the date of disease progression (PD)/relapse, as determined by the investigator, or death from any cause, whichever occurred earlier. A patient with PD/relapse must meet at least 1 of the following criteria: (1) Appearance of any new lesion \> 1.0 cm in the short axis during or at the end of therapy. (2) ≥ 50 % increase from nadir in the sum of the products of diameters (SPD, maximum diameter of a tumor x largest diameter perpendicular to the maximum diameter) of any previously involved nodes, in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be considered progressive disease, a lymph node with a diameter of the short axis \< 1.0 cm must increase by ≥ 50% to a size of 1.5 x 1.5 cm or \> 1.5 cm in the long axis. (3) ≥ 50 % increase in the greatest diameter of any previously identified node \> 1.0 cm in its short axis or in the SPD of more than 1 node.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Baseline to end of the study (up to 4 years, 4 months)	Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
Overall Response (OR) Assessed According to the Revised Response Criteria for Malignant Lymphoma	At the end of treatment (Cycle 8, up to 12 months)	OR = a complete response (CR), an unconfirmed CR, or a partial response (PR). CR = Complete disappearance of disease and disease-related symptoms. All lymph nodes and nodal masses regressed on computed tomography (CT) to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and \> 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical examination, normal size by imaging, and disappearance of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease.

Trial Locations

Locations (266)

Hopital Saint Jean; Hematologie; 🇫🇷 Perpignan, France

Uni of California - San Diego; Cancer Center & Dept of Medicine; 🇺🇸 La Jolla, California, United States

Kenmar Research Inst.; 🇺🇸 Whittier, California, United States

University of Colorado Cancer Center Department of Hematology; 🇺🇸 Aurora, Colorado, United States

Uni Medical Center; Division Of Hemotology/Oncology; 🇺🇸 Jacksonville, Florida, United States

Hopital De Haut Leveque; Hematologie Clinique; 🇫🇷 Pessac, France

Ch Lyon Sud; Hemato Secteur Jules Courmont; 🇫🇷 Pierre Benite, France

St. Joseph Mercy Hospital; Department of Oncology; 🇺🇸 Ann Arbor, Michigan, United States

Northeast Oncology Associates; 🇺🇸 Concord, North Carolina, United States

Forsyth Regional Cancer Center; Piedmont Hematology/Oncology Associates; 🇺🇸 Winston-Salem, North Carolina, United States

Northwest Medical Specialties B; 🇺🇸 Federal Way, Washington, United States

Hopital De La Miletrie; Hematologie Et Oncologie Medicale; 🇫🇷 Poitiers, France

Hospital Italiano; Haemathology; 🇦🇷 Buenos Aires, Argentina

HOSPITAL PRIVADO - CENTRO MEDICO DE CÓRDOBA; Dpto Oncología; 🇦🇷 Córdoba, Argentina

Greenslopes Private Hospital; Gallipoli Research Centre; 🇦🇺 Greenslopes, Queensland, Australia

Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology; 🇦🇺 Woolloongabba, Queensland, Australia

Frankston Hospital; Oncology/Haematology; 🇦🇺 Frankston, Victoria, Australia

Ashford Cancer Center Research; 🇦🇺 Kurralta Park, South Australia, Australia

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie; 🇦🇹 Wien, Austria

Centro Goiano de Oncologia - CGO; 🇧🇷 Goiania, GO, Brazil

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.; 🇦🇹 Salzburg, Austria

Hospital Nossa Senhora da Conceicao; 🇧🇷 Porto Alegre, RS, Brazil

Hospital das Clinicas - UFRGS; Hematologia; 🇧🇷 Porto Alegre, RS, Brazil

Hospital de Caridade de Ijui; Oncologia; 🇧🇷 Ijui, RS, Brazil

Hospital das Clinicas - UNICAMP; 🇧🇷 Campinas, SP, Brazil

Hospital das Clinicas - FMUSP; Hematologia; 🇧🇷 Sao Paulo, SP, Brazil

Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia; 🇧🇷 Santo Andre, SP, Brazil

Santa Casa de Misericordia de Sao Paulo; Hematologia e Hemoterapia; 🇧🇷 Sao Paulo, SP, Brazil

Windsor Regional Cancer Centre; 🇨🇦 Windsor, Ontario, Canada

Chuq - Hopital Hotel Dieu de Quebec; Oncology; 🇨🇦 Quebec City, Quebec, Canada

Cancer Hospital Chinese Academy of Medical Sciences.; 🇨🇳 Beijing, China

Beijing Cancer Hospital; 🇨🇳 Beijing, China

Beijing Union Hospital; 🇨🇳 Beijing, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China

Changhai Hospital of Shanghai; 🇨🇳 Shanghai, China

Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China

The Second Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, China

Tianjin Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China

First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, China

The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital); 🇨🇳 Xi'an, China

Fn Hr. Kralove; IV. Interni Hematologicka Klinika; 🇨🇿 Hradec Kralove, Czechia

Fakultni nemocnice Brno; Interni hematoonkologicka klinika; 🇨🇿 Brno, Czechia

VshEOBECNÁ FAKULTNÍ NEMOCNICE; I. INTERNI KLINIKA; 🇨🇿 Praha 2, Czechia

Fakultni nemocnice Olomouc; Hemato-onkologicka klinika; 🇨🇿 Olomouc, Czechia

Fakultni Nemocnice Plzen, Hematologicko-Onkologicke Oddeleni; 🇨🇿 Plzen - Lochotin, Czechia

Fakultní Nemocnice Královské Vinohrady; Hematologická Klinika; 🇨🇿 Praha, Czechia

Teodoro Maldonado Carbo Hospital; Oncology Service; 🇪🇨 Guayaquil, Ecuador

Clinique Claude Bernard; Onco Hematologie; 🇫🇷 Albi, France

Institut Bergonie; Hematologie Oncologie; 🇫🇷 Bordeaux, France

Centre Hospitalier Uni Ire; Service de Medecine D; 🇫🇷 Angers, France

Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie; 🇫🇷 Bordeaux, France

Chu Estaing; Cons Hemato Medecine Interne; 🇫🇷 Clermont Ferrand, France

Centre Francois Baclesse; Comite 2; 🇫🇷 Caen, France

Chu Site Du Bocage;Hematologie Clinique; 🇫🇷 Dijon, France

CH Dptal Les Oudairies; Hematologie Oncologie; 🇫🇷 La Roche Sur Yon, France

Hopital Albert Michallon; Oncologie; 🇫🇷 La Tronche, France

Clinique Victor Hugo; Chimiotherapie; 🇫🇷 Le Mans, France

Hopital Claude Huriez; Hematologie; 🇫🇷 Lille, France

Hopital Uni Ire Dupuytren; Hematologie; 🇫🇷 Limoges, France

Centre Leon Berard; Departement Oncologie Medicale; 🇫🇷 Lyon, France

Institut J Paolii Calmettes; Onco Hematologie 1; 🇫🇷 Marseille, France

Clinique Pont de Chaume; Oncologie Et Radiotherapie; 🇫🇷 Montauban, France

Hopital Saint Eloi; Hematologie Oncologie Medicale; 🇫🇷 Montpellier, France

Hopital de L'Archet; Hematologie Clinique; 🇫🇷 Nice, France

Polyclinique Kenval ; Radiotherapie Oncologie; 🇫🇷 Nimes, France

Institut Curie; Oncologie Medicale; 🇫🇷 Paris, France

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset); 🇫🇷 Paris, France

Ch Jacques Puel;Oncologie Medicale; 🇫🇷 Rodez, France

ICL; Hematologie; 🇫🇷 Saint-Priest en Jarez, France

Hopital Sud; Hematologie Clinique; 🇫🇷 Salouel, France

Hopital Purpan; Hematologie Clinique; 🇫🇷 Toulouse, France

Clinique Pasteur; Oncologie Medicale; 🇫🇷 Toulouse, France

Hopital Bretonneau; Hematologie Therapie Cellulaire; 🇫🇷 Tours, France

Hopitaux De Brabois; Hematologie Medecine Interne; 🇫🇷 Vandoeuvre Les Nancy, France

Institut Gustave Roussy; Unite D'Hematologie; 🇫🇷 Villejuif, France

Gesundheitszentrum St. Marien GmbH; Med. II, Hämatologie/Onkologie; 🇩🇪 Amberg, Germany

Charité; Onkologie & Hämatologie; 🇩🇪 Berlin, Germany

Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.; 🇩🇪 Berlin, Germany

DIAKO Ev. Diakonie-Krankenhaus Bremen GmbH; Med. Klinik II; Hämatologie und internistische Onkologie; 🇩🇪 Bremen, Germany

Klinikzentrum Mitte; Medizinische Klinik Gastroenterologie Haematologie / Onkologie; 🇩🇪 Dortmund, Germany

Carl-Thiem-Klinik Cottbus; Medizinische Klinik; 🇩🇪 Cottbus, Germany

St. Johannes Hospital; Abt. Innere Medizin; 🇩🇪 Dortmund, Germany

Krankenhaus Nordwest Medizinische Klinik; 🇩🇪 Frankfurt, Germany

St Antonius Hospital; Haematologie/Onkologie; 🇩🇪 Eschweiler, Germany

Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik; 🇩🇪 Greifswald, Germany

Klinik Fulda; Abt. Itz; 🇩🇪 Fulda, Germany

Georg-August-Uniklinik ; Zentrum Innere Medizin Abt. Hämatologie & Onkologie; 🇩🇪 Göttingen, Germany

Kath.Krankenhaus Hagen gem.GmbH St.-Marien-Hospital; 🇩🇪 Hagen, Germany

Asklepios Klinik St. Georg; Allgemeine Innere Medizin; 🇩🇪 Hamburg, Germany

Facharztzentrum Eppendorf, Studien GbR; 🇩🇪 Hamburg, Germany

Evang.Krankenhaus Abt. Hämatologie und Onkologie; 🇩🇪 Hamm, Germany

St.-Marien-Hospital Klinik Knappenstraße; Klinik für Hämatologie und Onkologie; 🇩🇪 Hamm, Germany

KRH Klinikum Siloah Medizinische Klinik III; 🇩🇪 Hannover, Germany

St. Bernward-Krankenhaus; 🇩🇪 Hildesheim, Germany

Universitaetsklinikum des Saarlandes; medizinische Klinik und Poliklinik; Innere Medizin I; 🇩🇪 Homburg/Saar, Germany

Städtisches Klinikum Karlsruhe gGmbH, II. Medizinische Klinik; 🇩🇪 Karlsruhe, Germany

Tagesklinik Landshut; Hämatologie/Onkologie; 🇩🇪 Landshut, Germany

Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog.; 🇩🇪 Leipzig, Germany

St. Vincentius Kliniken Ag; Medizinische Klinik Abt. 2; 🇩🇪 Karlsruhe, Germany

Klinikum St.Georg gGmbH Klinik für Internistische Onkologie und Hämotologie; 🇩🇪 Leipzig, Germany

Klinikum der Stadt Ludwigshafen; Medizinische Klinik A; 🇩🇪 Ludwigshafen, Germany

Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie; 🇩🇪 Lübeck, Germany

Märkische Kliniken GmbH, Klinikum Lüdenscheid; Hämatologie / Onkologie; 🇩🇪 Lüdenscheid, Germany

Otto von Guericke Uni Magdeburg Uniklinik; Hämatologie/Onkologie; 🇩🇪 Magdeburg, Germany

Klinikum Mannheim III. Medizinische Klinik; 🇩🇪 Mannheim, Germany

Klinikum Magdeburg gemeinnützige GmbH; Klinik Haematologie und Onkologie; 🇩🇪 Magdeburg, Germany

Klinikum der Universitaet Muenchen; Campus Großhadern; Medizinische Klinik III und Poliklinik; 🇩🇪 Muenchen, Germany

Klinikum Oldenburg gGmbH; Klinik für Onkologie und Hämatologie; 🇩🇪 Oldenburg, Germany

Westfälische Wilhelms-Universität Münster, Medizinische Klinik und Poliklinik A; 🇩🇪 Münster, Germany

St Marien Krankenhaus; Medizinische Klinik Iii; 🇩🇪 Siegen, Germany

Prosper-Hospital, Medizinische Klinik I; 🇩🇪 Recklinghausen, Germany

Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie; 🇩🇪 Trier, Germany

Krankenhaus der Barmherzigen Brüder Trier; Innere Medizin I, Hämatologie / Internistische Onkologie; 🇩🇪 Trier, Germany

Eberhard-Karls-Universität Tübingen; Medizinische Klinik I; 🇩🇪 Tübingen, Germany

Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.; 🇩🇪 Ulm, Germany

Helios Klinik Wuppertal; Medizinische Klinik I; 🇩🇪 Wuppertal, Germany

HSK Dr.-Horst-Schmidt-Kliniken; Innere Medizin I Kardiologie; Angiologie und Intensivmedizin; 🇩🇪 Wiesbaden, Germany

Kliniken St. Antonius; Zentrum Für Innere Medizin, Haematologie/Onkologie; 🇩🇪 Wuppertal, Germany

Fov. Onk. Egyesitett Szent Istvan es Szent Laszlo Korhaz; Dept Of Bone Marrow Transplant; 🇭🇺 Budapest, Hungary

A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna; 🇮🇹 Bologna, Emilia-Romagna, Italy

Ospedale Regionale Di Parma; Divisione Di Oncologia Medica; 🇮🇹 Parma, Emilia-Romagna, Italy

Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica; 🇮🇹 Aviano, Friuli-Venezia Giulia, Italy

Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia; 🇮🇹 Reggio Emilia, Emilia-Romagna, Italy

A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica; 🇮🇹 Udine, Friuli-Venezia Giulia, Italy

ASST DI MONZA; Ematologia; 🇮🇹 Monza, Lombardia, Italy

Irccs Policlinico San Matteo; Divisione Di Ematologia; 🇮🇹 Pavia, Lombardia, Italy

Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia; 🇮🇹 Campobasso, Molise, Italy

Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica; 🇮🇹 Bari, Puglia, Italy

Severance Hospital - Yonsei University; Medicine Dept.; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Centre; Oncology; 🇰🇷 Seoul, Korea, Republic of

Korean Cancer Center Hospital; Oncology; 🇰🇷 Seoul, Korea, Republic of

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

Uni of Auckland; Dept of Molecular Medicine & Haematology; 🇳🇿 Auckland, New Zealand

Christchurch Hospital; Canterbury Health Laboratories; 🇳🇿 Christchurch, New Zealand

Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie; 🇵🇱 Lublin, Poland

Republican Clinical Oncologic Dispensary of Republic Of Tatarstan; 🇷🇺 Kazan, Russian Federation

N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis; 🇷🇺 Moscow, Russian Federation

Hospital Universitario Marques de Valdecilla; Servicio de Hematologia; 🇪🇸 Santander, Cantabria, Spain

Hospital Universitario de Canarias;servicio de Oncologia; 🇪🇸 La Laguna, Tenerife, Spain

Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia; 🇪🇸 La Coruna, La Coruña, Spain

Hospital de Basurto; Servicio de Hematologia; 🇪🇸 Bilbao, Vizcaya, Spain

Hospital de Galdakano; 🇪🇸 Galdakano, Vizcaya, Spain

Hospital Clínic i Provincial; Servicio de Hematología y Oncología; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia; 🇪🇸 Barcelona, Spain

Complejo Hospitalario de Jaen- Hospital Universitario Medico Quirurgico; Servicio de Hematologia; 🇪🇸 Jaen, Spain

Hospital Universitari Vall d'Hebron; Servicio de Hematologia; 🇪🇸 Barcelona, Spain

Hospital Universitario la Paz; Servicio de Hematologia; 🇪🇸 Madrid, Spain

Hospital Universitario Clínico San Carlos; Servicio de Hematología; 🇪🇸 Madrid, Spain

Rajavithi Hospital; Medicine; 🇹🇭 Bangkok, Thailand

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia; 🇪🇸 Malaga, Spain

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia; 🇪🇸 Salamanca, Spain

Skånes University Hospital, Skånes Department of Onclology; 🇸🇪 Lund, Sweden

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia; 🇪🇸 Valencia, Spain

Länssjukhuset; Medicinkliniken; 🇸🇪 Sundsvall, Sweden

Hospital Universitario Virgen del Rocio; Servicio de Hematologia; 🇪🇸 Sevilla, Spain

Hospital Universitario Miguel Servet; Servicio Hematologia; 🇪🇸 Zaragoza, Spain

Skånes Universitetssjukhus; Kliniska Forskningsenheten Onkologimottagning medicinsk behandling; 🇸🇪 Malmö, Sweden

Akademiska sjukhuset, Onkologkliniken; 🇸🇪 Uppsala, Sweden

National Cancer Inst.; 🇹🇭 Bangkok, Thailand

Chang Gung Medical Foundation-Taipei; 🇨🇳 Taoyuan, Taiwan

Siriraj Hospital; Division of Hematology, Department of Medicine; 🇹🇭 Bangkok, Thailand

Birmingham Heartlands Hospital; Department of Haematology; 🇬🇧 Birmingham, United Kingdom

North Hampshire Hospital; Dept. of Haematology; 🇬🇧 Hampshire, United Kingdom

Leicester Royal Infirmary; Dept. of Medical Oncology; 🇬🇧 Leicester, United Kingdom

Hillingdon Hospital; 🇬🇧 Middx, United Kingdom

Bradford Royal Infirmary; Haematology Department; 🇬🇧 Bradford, United Kingdom

Princess Alexandra Hospital; Department of Haematology; 🇬🇧 Harlow, United Kingdom

Churchill Hospital; Oxford Cancer and Haematology Centre; 🇬🇧 Oxford, United Kingdom

St. George'S Hospital; Haematology; 🇬🇧 London, United Kingdom

Royal Liverpool Uni Hospital; Haematology; 🇬🇧 Liverpool, United Kingdom

Weston Park Hospital; Cancer Clinical Trials Centre; 🇬🇧 Sheffield, United Kingdom

The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology; 🇬🇧 Wolverhampton, United Kingdom

QEII HSC; Oncology; 🇨🇦 Halifax, Nova Scotia, Canada

Health Science Centre; 🇨🇦 St. John's, Newfoundland and Labrador, Canada

Tom Baker Cancer Centre; Dept of Medicine; 🇨🇦 Calgary, Alberta, Canada

Cross Cancer Institute ; Dept of Medical Oncology; 🇨🇦 Edmonton, Alberta, Canada

Fundaleu; Haematology; 🇦🇷 Buenos Aires, Argentina

Charleston Cancer Center; 🇺🇸 Charleston, South Carolina, United States

Hospital Britanico; Haematology; 🇦🇷 Buenos Aires, Argentina

Alfred Hospital; Bone Marrow Transplant Unit; 🇦🇺 Melbourne, Victoria, Australia

Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie; 🇨🇦 Greenfield Park, Quebec, Canada

Mcgill University - Royal Victoria Hospital; Oncology; 🇨🇦 Montreal, Quebec, Canada

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology; 🇨🇦 Montreal, Quebec, Canada

Peter Maccallum Cancer Institute; Medical Oncology; 🇦🇺 Melbourne, Victoria, Australia

Border Medical Oncology; Murray Valley Private Hospital; 🇦🇺 Wodonga, Victoria, Australia

Lkh-Univ. Klinikum Graz; Klinik Für Innere Medizin I; 🇦🇹 Graz, Austria

Hopital de L'Enfant-Jesus; Hematology; 🇨🇦 Quebec City, Quebec, Canada

Saskatoon Cancer Centre; Uni of Saskatoon Campus; 🇨🇦 Saskatoon, Saskatchewan, Canada

Organizacion Sanitas Internacional; 🇨🇴 Bogota, Colombia

Hospital Pablo Tobon Uribe; 🇨🇴 Medellin-Antioquia, Colombia

Instituto Cancerologia Medellin; Clinica Las Americas; 🇨🇴 Medellin, Colombia

Oncólogos de Occidente; 🇨🇴 Pereira, Colombia

Hospital Carlos Andrade Marin; Servicio de Oncología; 🇪🇨 Quito, Ecuador

Hospital Solca Quito; Oncologia; 🇪🇨 Quito, Ecuador

Georgios Papanikolaou Hospital; Hematology Department; 🇬🇷 Thessaloniki, Greece

University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology; 🇭🇺 Debrecen, Hungary

National Institute of Oncology, A Dept of Internal Medicine; 🇭🇺 Budapest, Hungary

Univ. Cattolica La Sapienza; Cattedra Di Ematologia; 🇮🇹 Roma, Lazio, Italy

Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia; 🇮🇹 Ascoli Piceno, Marche, Italy

Seamen' Hospital' Dept. of haematology; 🇱🇹 Klaipeda, Lithuania

Uni Hospital Santariskiu Clinic; Haematology; 🇱🇹 Vilnius, Lithuania

Hospital Pulau Pinang; 🇲🇾 Penang, Malaysia

Instituto Biomedico De Investigacion A.C.; 🇲🇽 Aguascalientes, Mexico

Hospital Español; Hematología Sala 19; 🇲🇽 Mexico City, Mexico

Col Instituto Tecnologico Y Estudios Superiores de Monterrey; 🇲🇽 Monterrey, Mexico

Hospital Universitario Dr. Jose E. Gonzalez; Haematology; 🇲🇽 Monterrey, Mexico

Centro Hemato Oncologico Paitilla; 🇵🇦 Panama City, Panama

Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica; 🇵🇪 Chiclayo, Peru

Hospital Nacional Edgardo Rebagliati Martins; Oncologia; 🇵🇪 Lima, Peru

Hospital Nacional Guillermo Almenara Irigoyen; Oncology; 🇵🇪 Lima, Peru

Instituto Nacional de Enfermedades Neoplasicas; 🇵🇪 Lima, Peru

Hospital Nacional LNS dela Policia Nacional del Perú. Unidad Onco; Deapartamento de Oncología; 🇵🇪 Lima, Peru

Cebu Cancer Institute; Perpetual Succour Hospital; 🇵🇭 Cebu, Philippines

National Kidney and Transplant Institute; Chemotherapy Unit; 🇵🇭 Diliman, Quezon City, Philippines

St Luke'S Medical Centre; Oncology; 🇵🇭 Quezon City, Philippines

Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny; 🇵🇱 Brzozów, Poland

Szpital Uniwersytecki W Krakowie; Klinika Hematologii; 🇵🇱 Krakow, Poland

Medical University School; Dept. of Haematology; 🇵🇱 Lodz, Poland

Zaklad Opieki Zdrowotnej Mswia; Oddzial Chemioterapii; 🇵🇱 Olsztyn, Poland

Samodzielny Publiczny Centralny Szpital Kliniczny; Haematology Dept.; 🇵🇱 Warszawa, Poland

Centralny Szpital Kliniczny Mswia; Klinika onkologii, hematologii i chorob wewnetrznych; 🇵🇱 Warszawa, Poland

Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Lymphoma Dept.; 🇵🇱 Warszawa, Poland

HUC; Servico de Hematologia; 🇵🇹 Coimbra, Portugal

IPO de Lisboa; Servico de Hematologia; 🇵🇹 Lisboa, Portugal

Hospital de Sao Joao; Servico de Hematologia Clinica; 🇵🇹 Porto, Portugal

Haematology Research Center; Haematology; 🇷🇺 Moscow, Russian Federation

Semashko Central Clinical Hospital Moscow; Hematology; 🇷🇺 Moscow, Russian Federation

Research Inst. of Hematology & Blood Transfusion ; Hematology; 🇷🇺 St Petersburg, Russian Federation

National Cancer Inst. ; Dept. of Chemotherapy; 🇸🇰 Bratislava, Slovakia

Hospital Mutua de Terrassa; Servicio de Hematologia; 🇪🇸 Terrassa, Barcelona, Spain

Universitätsspital Zürich; Klinik für Onkologie; 🇨🇭 Zürich, Switzerland

Veterans General Hospital; Division of Oncology; 🇨🇳 Taipei, Taiwan

Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology; 🇨🇳 Taipei, Taiwan

King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine; 🇹🇭 Bangkok, Thailand

Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine; 🇹🇭 Chiang Mai, Thailand

Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine; 🇹🇭 Khon Kaen, Thailand

General Hospital of Chinese PLA; Department of Hematology; 🇨🇳 Beijing, China

Cancer Care Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Fremantle Hospital; Haematology; 🇦🇺 Fremantle, Western Australia, Australia

University of Kansas Medical Center; Department of Hematology; 🇺🇸 Kansas City, Kansas, United States

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

Northwest Georgia Oncology Centers; 🇺🇸 Marietta, Georgia, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Uni of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Cancer Therapy & Research Center; 🇺🇸 San Antonio, Texas, United States

Rainier Physicians; 🇺🇸 Puyallup, Washington, United States

Royal Adelaide Hospital; Haematology, Institute of Medical Veterinary Science; 🇦🇺 Adelaide, South Australia, Australia

Moncton Hospital; 🇨🇦 Moncton, New Brunswick, Canada

Cancer Centre of Southeastern Ontario; Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

Credit Valley Hospital/Carlo Fidani Peel Regional Cancer Centre; 🇨🇦 Mississauga, Ontario, Canada

Toronto Sunnybrook Regional Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

University Health Network; Princess Margaret Hospital; Medical Oncology Dept; 🇨🇦 Toronto, Ontario, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico; 🇮🇹 Orbassano, Piemonte, Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1; 🇮🇹 Torino, Piemonte, Italy

Ospedale Ferrarotto; Divisione Di Ematologia; 🇮🇹 Via S. Sofia 78, Sicilia, Italy

Ospedale Santa Chiara; Unita Operativa Di Ematologia; 🇮🇹 Pisa, Toscana, Italy

Royal Hallamshire Hospital; Haematology Dept; 🇬🇧 Sheffield, United Kingdom

Hopital Pitie Salpetriere; Hematologie Clinique; 🇫🇷 Paris, France

Hospital Duran i Reynals; Servicio de Hematologia; 🇪🇸 Barcelona, Spain

Hospital Universitario la Fe; Servicio de Medicina Intena; 🇪🇸 Valencia, Spain

Northwest Medical Specialties; 🇺🇸 Tacoma, Washington, United States

Queen Elizabeth Hospital; Clinical Oncology; 🇭🇰 Hong Kong, Hong Kong

Queen Mary Hospital; Dept of Medicine; 🇭🇰 Hong Kong, Hong Kong

Fujian Cancer Hospital; 🇨🇳 Fuzhou, China