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A Safety and Efficacy Study of Obinutuzumab Alone or in Combination With Chemotherapy in Participants With Chronic Lymphocytic Leukemia

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bendamustine
Chlorambucil
Cyclophosphamide
Fludarabine
Obinutuzumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Previously untreated documented CLL according to National Cancer Institute/international workshop on CLL (NCI/iwCLL) criteria OR relapsed and/or refractory documented CLL participants requiring treatment according to NCI/iwCLL criteria; participants with up to 3 relapses are eligible
  • Refractory participants if last treatment was with single-agent therapy, single-agent chemotherapy, or single-agent antibody
  • Participants with 17p-deletion and/or p53 mutation may be included at the investigator's discretion
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy greater than (>) 6 months according to the investigator's opinion
  • Adequate hematological function

Exclusion Criteria:

  • Participants who have received more than 3 previous CLL treatment lines
  • Documented transformation of CLL to aggressive lymphoma (Richter's transformation)
  • Participants who are refractory to immunochemotherapy
  • Participants with abnormal laboratory values
  • One or more individual organ/system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition, excluding the eyes, ears, nose, throat and larynx organ systems
  • Participants with a history of progressive multifocal leukoencephalopathy (PML)
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  • Known hypersensitivity to the study drugs
  • History of prior malignancy unless the malignancy has been treated with a curative intent and in remission without treatment for greater than or equal to (>/=) 5 years prior to enrollment and with the exception of curatively-treated basal cell carcinoma, squamous cell carcinoma of the skin, low grade in situ carcinoma of the cervix, or low grade, early stage localized prostate cancer treated surgically with curative intent
  • Regular treatment with corticosteroids during the 28 days prior to the start of Cycle 1, Day 1, unless administered for indications other than CLL at a dose equivalent to less than or equal to (</=) 30 milligrams per day (mg/day) prednisone
  • Regular treatment with immunosuppressive medications following previous organ transplantation
  • Evidence of significant, uncontrolled concomitant diseases
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) or a major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization within 28 days prior to the start of Cycle 1, Day 1
  • Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1
  • Major surgery (within 28 days prior to the start of Cycle 1, Day 1), other than for diagnosis
  • Positive for chronic hepatitis B, hepatitis C, human T-lymphotropic virus 1 (HTLV 1) or human immunodeficiency virus (HIV) infection
  • Pregnant or lactating women
  • Fertile men or women of childbearing potential
  • Participation in another clinical trial with drug intervention within 28 days prior to start of Cycle 1, Day 1 and during the study

Sites / Locations

  • Hospital Iturraspe
  • Hospital Erasme; Neurologie
  • Cliniques Universitaires St-Luc
  • Jessa Zkh (Campus Virga Jesse)
  • CHU Sart-Tilman
  • Sint Augustinus Wilrijk
  • University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept
  • University Clinical Center Sarajevo, Clinic for Hematology
  • Hospital das Clinicas - UFRGS
  • Hospital de Cancer de Barretos
  • Hospital Amaral Carvalho
  • Instituto de Ensino e Pesquisa Sao Lucas - IEP
  • Hospital Sirio Libanes; Centro de Oncologia
  • Hospital Estadual do Servidor Publico; Hematologia
  • Hospital das Clinicas - FMUSP; Hematologia
  • Hospital Santa Marcelina;Oncologia
  • Cancer Care Manitoba
  • Regional health authority A vitalite health network
  • Queen Elizabeth II Health Sciences Centre; Oncology
  • Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials
  • Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
  • Hopital Maisonneuve- Rosemont; Oncology
  • Centre de sante et de services sociaux Rimouski Neigette
  • Saskatoon Cancer Centre; Uni of Saskatoon Campus
  • CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie
  • Cairo University Hospital Al Kasr El Ainy
  • National Cancer Institute
  • North Estonia Regional Hospital; Hematology
  • Tartu Uni Hospital; Hematology - Oncology Clinic
  • Kuopio University Hospital
  • Tampere University Hospital; Hematology
  • Turku Uni Central Hospital; Dept of Internal Medicine
  • Hotel Dieu; Medecine D
  • Ch Victor Dupouy; Hematologie
  • Hopital Augustin Morvan; Hematologie
  • Hopital Cote De Nacre; Hematologie Biologique
  • Chu Estaing; Hematologie Clinique Adultes
  • Hopital Henri Mondor; Hematologie Clinique
  • Chu Site Du Bocage;Hematologie Clinique
  • Centre Hospitalier Departemental Les Oudairies
  • Ch Du Mans; Medecine Hematologie Oncologie
  • Hopital Claude Huriez; Hematologie
  • Hopital Uni Ire Dupuytren; Hematologie
  • Hopital Saint Eloi; Hematologie Oncologie Medicale
  • Hopital Emile Muller; Hematologie
  • Hopital Hotel Dieu Et Hme;Hopital De Jour
  • Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
  • Hopital Saint Antoine; Hematologie Clinique
  • Hopital Pitie Salpetriere; Hematologie Clinique
  • Hopital Saint Jean; Hematologie
  • Hopital De Haut Leveque; Hematologie Clinique
  • Ch Lyon Sud; Hemato Secteur Jules Courmont
  • Centre Hospitalier René Dubos; Hematologie
  • Hopital Robert Debre; Hematologie Clinique
  • Centre Henri Becquerel; Hematologie
  • Centre Hospitalier de Saint Brieuc - Hôpital Yves Le Foll
  • Hopital Bretonneau; Hematologie Therapie Cellulaire
  • Hämatologisch-onkologische Praxis Dr. med. - Heinrich, - Bangerter
  • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
  • Gemeinschaftspraxis; Prof. Dr. Michael Kiehl und Dr.med. Wolfgang Stein
  • Onkologisches Zentrum am Bethanien-Kankenhaus
  • Dres.Andreas Ammon und Dirk Meyer
  • OncoResearch Lerchenfeld GmbH
  • Onkologische Schwerpunktpraxis Lübeck
  • Onkologische Gemeinschaftspraxis
  • Kliniken Ostalb, Stauferklinikum Schwäbisch-Gmünd; Zentrum für Innere Medizin
  • Dres. Hans-Dieter Schick Dorothea Schick Burkhard Schmidt u.w.
  • Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura
  • eps - early phase GmbH
  • Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie
  • Schwerpunktpraxis & Tagesklinik f. Hämatologie & Onkologie Regensdorf / Schwandorf / Wörth
  • Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
  • Onkologische Schwerpunktpraxis Dres. Rudolf Schlag und Björn Schöttker
  • General Hospital of Athens Evangelismos; Hematology
  • Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine
  • Laiko General Hospital; Hematology Clinic
  • University Hospital of Ioannina; Hematology
  • Georgios Papanikolaou Hospital; Hematology Department
  • Mater Misericordiae Uni Hospital; Oncology
  • University Hospital Limerick - Oncology
  • Waterford Regional Hospital; Department Of Medical Oncology
  • Soroka Medical Center; Hematology Deptartment
  • Bnei-Zion Medical Center; Hematology Dept
  • Hadassah Ein Karem Hospital; Haematology
  • Kaplan Medical Center
  • Ichilov Sourasky Medical Center; Heamatology
  • Az. Osp. Pugliese; Divisione de Ematologia
  • Ospedale Cardarelli; Divisione Di Ematologia
  • Arcispedale S. Anna; Sezione Di Ematologia
  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
  • A.O. Universitaria Policlinico Di Modena; Ematologia
  • AUSL di Piacenza - Ospedale "Guglielmo da Saliceto";U.O. Ematologia
  • Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
  • Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia
  • Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
  • Uni Degli Studi Di Genova; 1A Divisione Di Ematologia
  • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
  • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
  • Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
  • Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I
  • Azienda ospedaliera oo rr di foggi; Hematology
  • Ospedale Vito Fazzi; Div. Oncoematologia
  • Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.
  • Azienda USL 6 Livorno - P.O. Livorno; U.O. Ematologia Clinica
  • Pusan University Hospital
  • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Samsung Medical Centre; Division of Hematology/Oncology
  • RECUH, Oncology Centre of Latvia; Clinic of Chemotherapy and Heamatology
  • Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
  • Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center
  • Hospital General De Culiacan; Servicio De Hematologia
  • Hospital General de México; Haematology
  • Centro Medico Nacional Sxxi - Imss; Haematology
  • Hospital Universitario Dr. Jose E. Gonzalez; Haematology
  • Centro de Estudios Clinicos de Queretaro (CECLIQ)
  • University Clinic of Hematology Skopje, Hospital Care Department
  • Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
  • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
  • Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej
  • Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny
  • Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula
  • IPO do Porto; Servico de Onco-Hematologia
  • Policlinica de Diagnostic Rapid
  • Spitalul Clinic Judetean de Urgenta Brasov; Clinica de Hematologie
  • Spitalul Clinic Coltea; Clinica de Hematologie
  • Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
  • FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
  • Vladimirskiy Regional Scientific Research Inst. ; Hematology
  • Almazov Federal Heart, Blood and Endocrinilogy Centre; Hematology department
  • Regional Oncology Center
  • Institute of Hematology
  • Fakultna Nemocnica Roosevelta; Dept. of Haematology
  • National Oncology Inst. ; Dept. of Haematology
  • Hospital Celje; Haematology Dept
  • Clinical Center Ljubljana; Haematology Dept
  • Hospital Maribor; Haematology Dept
  • Hospital De Txagorritxu; Servicio de Hematologia
  • Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
  • Hospital Universitario Son Espases
  • Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia
  • Hospital Quiron de Madrid; Servicio de Hematologia
  • Hospital San Pedro De Alcantara; Servicio de Hematologia
  • Hospital Universitario Reina Sofia; Servicio de Hematologia
  • Hospital Infanta Leonor; Servicio de Hematologia
  • Hospital Universitario Clínico San Carlos; Servicio de Hematología
  • Complejo Hospitalario Universitario de Ourense, Servicio de Hematologia
  • Hospital Universitario Virgen del Rocio; Servicio de Hematologia
  • Hospital Universitario la Fe; Servicio de Hematologia
  • Universitetssjukhuset i Linköping, Hematologkliniken
  • Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders
  • Uddevalla Sjukhus; Medicinkliniken
  • Akademiska Sjukhuset
  • Kantonsspital Aarau; Zentrum Für Onkologie, Hämatologie & Transfusionsmedizin
  • Universitätsspital Basel; Hämatologie
  • Istituto Oncologico della Svizzera Italiana (IOSI)
  • Kantonsspital Graubünden;Onkologie und Hämatologie
  • HUG; Hématologie
  • Luzerner Kantonsspital, Hämatologie
  • OnkoZentrum Zuerich
  • King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine
  • Ramathibodi Hospital; Division of Hematology, Department of Medicine
  • Siriraj Hospital; Division of Hematology, Department of Medicine
  • Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine
  • Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine
  • Cukurova Uni ; Hematology
  • Ankara Numune Egitim Ve Arastirma Hastanesi; Hematoloji Klinigi
  • Ankara University; Hematology
  • Pamukkale Uni. Med. Fac.
  • Gaziantep University Medical School; Hematology
  • Istanbul Uni Capa Hospital; Hematology
  • Dokuz Eylul Uni ; Hematology
  • Erciyes Uni ; Hematology
  • Ondokuzmayis University Medical Faculty Heamatology Department
  • Karadeniz Technical Uni School of Medicine; Hematology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Obinutuzumab

Arm Description

Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Number of Participants With Adverse Events of Special Interest (AESIs)
The following AEs were defined as AESIs: AEs with the preferred term Tumour Lysis Syndrome (TLS), Infusion-Related Reactions (IRRs) defined as AEs that occurred during or within 24 hours of the completion of obinutuzumab infusion and were assessed as related to obinutuzumab by the Investigator, Infections defined as AEs from System Organ Class (SOC) "Infections and infestations" and AEs with the preferred term Neutropenia. Reported are number of participants with total AESIs, IRRs, Infections, Neutropenia and TLS.
Number of Participants With Adverse Events of Particular Interest (AEPIs)
The following AEs were defined as AEPIs: AEs with the preferred term Progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation defined as AEs with preferred term containing "Hepatitis B" or "hepatitis acute", thrombocytopenia defined via Roche MedDRA basket subgroup "haematopoietic thrombocytopenia", second malignancies defined as AEs from the SOC "Neoplasms benign, malignant and unspecified" starting 6 months after the first study drug intake, second malignancies based on standardised MedDRA queries (SMQ) starting 6 months after the first study drug intake based on the MedDRA SMQ "Malignant or unspecified tumours", in which benign neoplasms are not included, Cardiac events including AEs from the SOC "Cardiac disorders", and hemorrhagic events defined via Roche MedDRA basket subgroup "Haemorrhagic events". Reported are number of participants with total AEPIs and each of the AEPI categories.

Secondary Outcome Measures

Percentage of Participants With Overall Response (OR) at Final Response Assessment (FRA)
OR: percentage of participants with complete response (CR) or CR with incomplete marrow recovery (CRi), or partial response (PR), as determined by the investigator based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) tumor response criteria. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. Cri: CR with persistent cytopenia. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin.
Percentage of Participants With Minimal Residual Disease (MRD)-Negativity as Assessed by Flow Cytometry
MRD-negativity was defined as the presence of less than 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes in blood and bone marrow as assessed by flow cytometry 3 months after last dose of study treatment (i.e. at final response assessment [FRA] visit).
Percentage of Participants With Best Overall Response (BOR)
BOR was defined as the percentage of participants with the best response obtained throughout the trial with CR, CRi, or PR, as determined by the investigator based on IWCLL tumor response criteria. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. Cri: CR with persistent cytopenia. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin.
Median Time to Progression-Free Survival (PFS)
Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on IWCLL tumor response criteria or died from any cause, whichever occurred first. PD: at least one of the following: >/= 50% increase in the absolute number of circulating lymphocytes to at least 5,000/mcL, appearance of new palpable lymph nodes, >/= 50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, >/= 50% increase in the enlargement of the liver and/or spleen, transformation to more aggressive histology, progression of any cytopenia, decrease of hemoglobin levels by more than 20 g/L or to less than 100 g/L, decrease of platelet counts by more than 50% or to less than 100,000 /mcL, decrease of neutrophil counts by more than 50% or to less than 1,000/mcL.
Median Time to Response (TTR)
Kaplan Meier estimate of median TTR was defined as the time at which half of the participants reached CR or PR based on IWCLL tumor response criteria. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin.
Median Time to Event-Free Survival (EFS)
Kaplan Meier estimate of median EFS is the time at which half of the participants have progressed as assessed by investigator based on IWCLL tumor response criteria, or have initiated a non-protocol-specified anti-leukemia therapy or died, whichever occurs first. PD: at least 1 of the following: >/= 50% increase in absolute number of circulating lymphocytes to at least 5,000/mcL, appearance of new palpable lymph nodes, >/= 50% increase in longest diameter of any previous site of clinically significant lymphadenopathy, >/= 50% increase in enlargement of liver and/or spleen, transformation to more aggressive histology, progression of any cytopenia, decrease of hemoglobin levels by more than 20 g/L or to less than 100 g/L, decrease of platelet counts by more than 50% or to less than 100,000 /mcL, decrease of neutrophil counts by more than 50% or to less than 1,000/mcL.
Median Time to Overall Survival (OS)
Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death.
Median Time to New Anti-Leukemia Therapy (TTNT)
Kaplan Meier estimate of median TTNT was defined as the time at which half of the participants have initiated a new anti-leukemic therapy.
Median Time to Duration of Response (DoR)
Kaplan Meier estimate of median DoR was defined as the time at which half of the responding (PR or CR) participants had progressed (PD) or died from any cause, whichever occurred first. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. PD: as defined in the description for Event-Free Survival outcome measure.

Full Information

First Posted
July 19, 2013
Last Updated
October 24, 2019
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01905943
Brief Title
A Safety and Efficacy Study of Obinutuzumab Alone or in Combination With Chemotherapy in Participants With Chronic Lymphocytic Leukemia
Official Title
A Multicenter, Open-Label, Single-Arm, Phase IIIb, International Study Evaluating the Safety of Obinutuzumab Alone or in Combination With Chemotherapy in Patients With Previously Untreated or Relapsed/Refractory Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
November 4, 2013 (Actual)
Primary Completion Date
December 29, 2016 (Actual)
Study Completion Date
October 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This multicenter, open-label, single-arm study will evaluate the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in participants with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL). This is a Post-Authorization Safety Study. Participants will receive 6 cycles of single-agent obinutuzumab or obinutuzumab in combination with chemotherapy at the investigator's discretion. Each participant will be followed until 30 months after the last participant has been enrolled. Total length of the study is anticipated to be approximately 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
979 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Obinutuzumab
Arm Type
Experimental
Arm Description
Participants will receive obinutuzumab either alone as single agent or in combination with chemotherapy (Fludarabine/Cyclophosphamide [FC], Bendamustine or Chlorambucil) at the investigator's discretion. Each cycle is of 28-days duration.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Intervention Description
Bendamustine: 90 milligram per millilitre square (mg/m^2) IV over 60 minutes once daily (QD) Day 1-2 in participants previously untreated or 70 mg/m^2 I.V. over 60 minutes QD Day 1-2 in participants with relapsed/refractory disease. In non-fit participants only, investigators may opt at their own discretion to use lower initial doses of bendamustine, i.e., bendamustine 70 mg/m^2 in previously untreated participants, and bendamustine 50 mg/m^2 in relapsed/refractory subjects (over 60 minutes qd Day 1-2 for each administration).
Intervention Type
Drug
Intervention Name(s)
Chlorambucil
Intervention Description
Chlorambucil 0.5 mg/kg p.o. qd on Day 1 and Day 15 in non-fit participants only.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 250 mg/m^2 I.V. over 15-30 minutes qd Day 1-3 or Cyclophosphamide 250 mg/m^2 p.o. QD Day 1-3 in fit participants only.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine 25 mg/m^2 I.V. over 30 minutes QD Day 1-3 or Fludarabine 40 mg/m^2 per os (p.o.) QD Day 1-3 in fit participants only.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Other Intervention Name(s)
Gazyva®, RO5072759
Intervention Description
Participants will receive obinutuzumab 1000 mg IV infusion on Days 1/2 (dose split over 2 consecutive days; 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1, and on Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle is of 28-days duration.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Time Frame
Baseline up to time of primary completion (3 years)
Title
Number of Participants With Adverse Events of Special Interest (AESIs)
Description
The following AEs were defined as AESIs: AEs with the preferred term Tumour Lysis Syndrome (TLS), Infusion-Related Reactions (IRRs) defined as AEs that occurred during or within 24 hours of the completion of obinutuzumab infusion and were assessed as related to obinutuzumab by the Investigator, Infections defined as AEs from System Organ Class (SOC) "Infections and infestations" and AEs with the preferred term Neutropenia. Reported are number of participants with total AESIs, IRRs, Infections, Neutropenia and TLS.
Time Frame
Baseline up to time of primary completion (3 years)
Title
Number of Participants With Adverse Events of Particular Interest (AEPIs)
Description
The following AEs were defined as AEPIs: AEs with the preferred term Progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation defined as AEs with preferred term containing "Hepatitis B" or "hepatitis acute", thrombocytopenia defined via Roche MedDRA basket subgroup "haematopoietic thrombocytopenia", second malignancies defined as AEs from the SOC "Neoplasms benign, malignant and unspecified" starting 6 months after the first study drug intake, second malignancies based on standardised MedDRA queries (SMQ) starting 6 months after the first study drug intake based on the MedDRA SMQ "Malignant or unspecified tumours", in which benign neoplasms are not included, Cardiac events including AEs from the SOC "Cardiac disorders", and hemorrhagic events defined via Roche MedDRA basket subgroup "Haemorrhagic events". Reported are number of participants with total AEPIs and each of the AEPI categories.
Time Frame
Baseline up to time of primary completion (3 years)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Overall Response (OR) at Final Response Assessment (FRA)
Description
OR: percentage of participants with complete response (CR) or CR with incomplete marrow recovery (CRi), or partial response (PR), as determined by the investigator based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) tumor response criteria. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. Cri: CR with persistent cytopenia. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin.
Time Frame
3 months after the last dose of study treatment (up to approximately 5 years)
Title
Percentage of Participants With Minimal Residual Disease (MRD)-Negativity as Assessed by Flow Cytometry
Description
MRD-negativity was defined as the presence of less than 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes in blood and bone marrow as assessed by flow cytometry 3 months after last dose of study treatment (i.e. at final response assessment [FRA] visit).
Time Frame
3 months after the last dose of study treatment (up to approximately 5 years)
Title
Percentage of Participants With Best Overall Response (BOR)
Description
BOR was defined as the percentage of participants with the best response obtained throughout the trial with CR, CRi, or PR, as determined by the investigator based on IWCLL tumor response criteria. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. Cri: CR with persistent cytopenia. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin.
Time Frame
Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years)
Title
Median Time to Progression-Free Survival (PFS)
Description
Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on IWCLL tumor response criteria or died from any cause, whichever occurred first. PD: at least one of the following: >/= 50% increase in the absolute number of circulating lymphocytes to at least 5,000/mcL, appearance of new palpable lymph nodes, >/= 50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, >/= 50% increase in the enlargement of the liver and/or spleen, transformation to more aggressive histology, progression of any cytopenia, decrease of hemoglobin levels by more than 20 g/L or to less than 100 g/L, decrease of platelet counts by more than 50% or to less than 100,000 /mcL, decrease of neutrophil counts by more than 50% or to less than 1,000/mcL.
Time Frame
Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years)
Title
Median Time to Response (TTR)
Description
Kaplan Meier estimate of median TTR was defined as the time at which half of the participants reached CR or PR based on IWCLL tumor response criteria. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin.
Time Frame
Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years)
Title
Median Time to Event-Free Survival (EFS)
Description
Kaplan Meier estimate of median EFS is the time at which half of the participants have progressed as assessed by investigator based on IWCLL tumor response criteria, or have initiated a non-protocol-specified anti-leukemia therapy or died, whichever occurs first. PD: at least 1 of the following: >/= 50% increase in absolute number of circulating lymphocytes to at least 5,000/mcL, appearance of new palpable lymph nodes, >/= 50% increase in longest diameter of any previous site of clinically significant lymphadenopathy, >/= 50% increase in enlargement of liver and/or spleen, transformation to more aggressive histology, progression of any cytopenia, decrease of hemoglobin levels by more than 20 g/L or to less than 100 g/L, decrease of platelet counts by more than 50% or to less than 100,000 /mcL, decrease of neutrophil counts by more than 50% or to less than 1,000/mcL.
Time Frame
Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years)
Title
Median Time to Overall Survival (OS)
Description
Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death.
Time Frame
Baseline until death (Approximately up to 5 years)
Title
Median Time to New Anti-Leukemia Therapy (TTNT)
Description
Kaplan Meier estimate of median TTNT was defined as the time at which half of the participants have initiated a new anti-leukemic therapy.
Time Frame
Baseline until end of study (up to approximately 5 years)
Title
Median Time to Duration of Response (DoR)
Description
Kaplan Meier estimate of median DoR was defined as the time at which half of the responding (PR or CR) participants had progressed (PD) or died from any cause, whichever occurred first. PR: >/= 50% decrease in peripheral blood lymphocyte count AND >/= 50% reduction in lymphadenopathy OR >/= 50% reduction of liver enlargement OR >/= 50% reduction of spleen PLUS one of the following: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L OR >/= 50% increase in neutrophils, platelets or hemoglobin. CR: Peripheral blood lymphocytes 4,000/mcL, no significant lymphadenopathy, no hepatomegaly and splenomegaly, no disease symptoms, blood counts: neutrophils >1,500/mcL, platelets > 100,000/mcL, hemoglobin > 110 g/L and bone marrow normocellular for age. PD: as defined in the description for Event-Free Survival outcome measure.
Time Frame
Baseline, Day 85, end of treatment or early termination, and follow-up, assessed up to disease progression or death, whichever occurs first (up to approximately 5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Previously untreated documented CLL according to National Cancer Institute/international workshop on CLL (NCI/iwCLL) criteria OR relapsed and/or refractory documented CLL participants requiring treatment according to NCI/iwCLL criteria; participants with up to 3 relapses are eligible Refractory participants if last treatment was with single-agent therapy, single-agent chemotherapy, or single-agent antibody Participants with 17p-deletion and/or p53 mutation may be included at the investigator's discretion Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy greater than (>) 6 months according to the investigator's opinion Adequate hematological function Exclusion Criteria: Participants who have received more than 3 previous CLL treatment lines Documented transformation of CLL to aggressive lymphoma (Richter's transformation) Participants who are refractory to immunochemotherapy Participants with abnormal laboratory values One or more individual organ/system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition, excluding the eyes, ears, nose, throat and larynx organ systems Participants with a history of progressive multifocal leukoencephalopathy (PML) History of severe allergic or anaphylactic reactions to monoclonal antibody therapy Known hypersensitivity to the study drugs History of prior malignancy unless the malignancy has been treated with a curative intent and in remission without treatment for greater than or equal to (>/=) 5 years prior to enrollment and with the exception of curatively-treated basal cell carcinoma, squamous cell carcinoma of the skin, low grade in situ carcinoma of the cervix, or low grade, early stage localized prostate cancer treated surgically with curative intent Regular treatment with corticosteroids during the 28 days prior to the start of Cycle 1, Day 1, unless administered for indications other than CLL at a dose equivalent to less than or equal to (</=) 30 milligrams per day (mg/day) prednisone Regular treatment with immunosuppressive medications following previous organ transplantation Evidence of significant, uncontrolled concomitant diseases Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) or a major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization within 28 days prior to the start of Cycle 1, Day 1 Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1 Major surgery (within 28 days prior to the start of Cycle 1, Day 1), other than for diagnosis Positive for chronic hepatitis B, hepatitis C, human T-lymphotropic virus 1 (HTLV 1) or human immunodeficiency virus (HIV) infection Pregnant or lactating women Fertile men or women of childbearing potential Participation in another clinical trial with drug intervention within 28 days prior to start of Cycle 1, Day 1 and during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Iturraspe
City
Santa Fé
ZIP/Postal Code
3000
Country
Argentina
Facility Name
Hospital Erasme; Neurologie
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Cliniques Universitaires St-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Jessa Zkh (Campus Virga Jesse)
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
CHU Sart-Tilman
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Sint Augustinus Wilrijk
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept
City
Banja Luka
ZIP/Postal Code
88000
Country
Bosnia and Herzegovina
Facility Name
University Clinical Center Sarajevo, Clinic for Hematology
City
Sarajevo
ZIP/Postal Code
71000
Country
Bosnia and Herzegovina
Facility Name
Hospital das Clinicas - UFRGS
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Hospital de Cancer de Barretos
City
Barretos
State/Province
SP
ZIP/Postal Code
14784-400
Country
Brazil
Facility Name
Hospital Amaral Carvalho
City
Jau
State/Province
SP
ZIP/Postal Code
17210-120
Country
Brazil
Facility Name
Instituto de Ensino e Pesquisa Sao Lucas - IEP
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01236-030
Country
Brazil
Facility Name
Hospital Sirio Libanes; Centro de Oncologia
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01308-050
Country
Brazil
Facility Name
Hospital Estadual do Servidor Publico; Hematologia
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04029-000
Country
Brazil
Facility Name
Hospital das Clinicas - FMUSP; Hematologia
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Hospital Santa Marcelina;Oncologia
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
08270-070
Country
Brazil
Facility Name
Cancer Care Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Facility Name
Regional health authority A vitalite health network
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C 8X3
Country
Canada
Facility Name
Queen Elizabeth II Health Sciences Centre; Oncology
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials
City
Barrie
State/Province
Ontario
ZIP/Postal Code
L4M 6M2
Country
Canada
Facility Name
Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Hopital Maisonneuve- Rosemont; Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Centre de sante et de services sociaux Rimouski Neigette
City
Rimouski
State/Province
Quebec
ZIP/Postal Code
G5L 5T1
Country
Canada
Facility Name
Saskatoon Cancer Centre; Uni of Saskatoon Campus
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada
Facility Name
CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Cairo University Hospital Al Kasr El Ainy
City
Cairo
ZIP/Postal Code
11559
Country
Egypt
Facility Name
National Cancer Institute
City
Cairo
ZIP/Postal Code
11796
Country
Egypt
Facility Name
North Estonia Regional Hospital; Hematology
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Tartu Uni Hospital; Hematology - Oncology Clinic
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Kuopio University Hospital
City
Kuopio
ZIP/Postal Code
70211
Country
Finland
Facility Name
Tampere University Hospital; Hematology
City
Tampere
ZIP/Postal Code
33521
Country
Finland
Facility Name
Turku Uni Central Hospital; Dept of Internal Medicine
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Hotel Dieu; Medecine D
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
Ch Victor Dupouy; Hematologie
City
Argenteuil
ZIP/Postal Code
95107
Country
France
Facility Name
Hopital Augustin Morvan; Hematologie
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Hopital Cote De Nacre; Hematologie Biologique
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Chu Estaing; Hematologie Clinique Adultes
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
Hopital Henri Mondor; Hematologie Clinique
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Chu Site Du Bocage;Hematologie Clinique
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Centre Hospitalier Departemental Les Oudairies
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
Facility Name
Ch Du Mans; Medecine Hematologie Oncologie
City
Le Mans
ZIP/Postal Code
72037
Country
France
Facility Name
Hopital Claude Huriez; Hematologie
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital Uni Ire Dupuytren; Hematologie
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hopital Saint Eloi; Hematologie Oncologie Medicale
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Emile Muller; Hematologie
City
Mulhouse
ZIP/Postal Code
68070
Country
France
Facility Name
Hopital Hotel Dieu Et Hme;Hopital De Jour
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Hopital Saint Antoine; Hematologie Clinique
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Hopital Pitie Salpetriere; Hematologie Clinique
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Hopital Saint Jean; Hematologie
City
Perpignan
ZIP/Postal Code
66046
Country
France
Facility Name
Hopital De Haut Leveque; Hematologie Clinique
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Ch Lyon Sud; Hemato Secteur Jules Courmont
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Hospitalier René Dubos; Hematologie
City
Pontoise
ZIP/Postal Code
95300
Country
France
Facility Name
Hopital Robert Debre; Hematologie Clinique
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Centre Henri Becquerel; Hematologie
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Centre Hospitalier de Saint Brieuc - Hôpital Yves Le Foll
City
St Brieuc
ZIP/Postal Code
22027
Country
France
Facility Name
Hopital Bretonneau; Hematologie Therapie Cellulaire
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Hämatologisch-onkologische Praxis Dr. med. - Heinrich, - Bangerter
City
Augsburg
ZIP/Postal Code
86150
Country
Germany
Facility Name
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Gemeinschaftspraxis; Prof. Dr. Michael Kiehl und Dr.med. Wolfgang Stein
City
Frankfurt an der Oder
ZIP/Postal Code
15236
Country
Germany
Facility Name
Onkologisches Zentrum am Bethanien-Kankenhaus
City
Frankfurt
ZIP/Postal Code
60389
Country
Germany
Facility Name
Dres.Andreas Ammon und Dirk Meyer
City
Göttingen
ZIP/Postal Code
37073
Country
Germany
Facility Name
OncoResearch Lerchenfeld GmbH
City
Hamburg
ZIP/Postal Code
22081
Country
Germany
Facility Name
Onkologische Schwerpunktpraxis Lübeck
City
Lübeck
ZIP/Postal Code
23562
Country
Germany
Facility Name
Onkologische Gemeinschaftspraxis
City
Magdeburg
ZIP/Postal Code
39104
Country
Germany
Facility Name
Kliniken Ostalb, Stauferklinikum Schwäbisch-Gmünd; Zentrum für Innere Medizin
City
Mutlangen
ZIP/Postal Code
73557
Country
Germany
Facility Name
Dres. Hans-Dieter Schick Dorothea Schick Burkhard Schmidt u.w.
City
München
ZIP/Postal Code
81241
Country
Germany
Facility Name
Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura
City
Neunkirchen/Saar
ZIP/Postal Code
66538
Country
Germany
Facility Name
eps - early phase GmbH
City
Pößneck
ZIP/Postal Code
07381
Country
Germany
Facility Name
Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie
City
Recklinghausen
ZIP/Postal Code
45659
Country
Germany
Facility Name
Schwerpunktpraxis & Tagesklinik f. Hämatologie & Onkologie Regensdorf / Schwandorf / Wörth
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Onkologische Schwerpunktpraxis Dres. Rudolf Schlag und Björn Schöttker
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
General Hospital of Athens Evangelismos; Hematology
City
Athens
ZIP/Postal Code
106 76
Country
Greece
Facility Name
Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Laiko General Hospital; Hematology Clinic
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
University Hospital of Ioannina; Hematology
City
Ioannina
ZIP/Postal Code
455 00
Country
Greece
Facility Name
Georgios Papanikolaou Hospital; Hematology Department
City
Thessaloniki
ZIP/Postal Code
570 10
Country
Greece
Facility Name
Mater Misericordiae Uni Hospital; Oncology
City
Dublin
ZIP/Postal Code
7
Country
Ireland
Facility Name
University Hospital Limerick - Oncology
City
Limerick
Country
Ireland
Facility Name
Waterford Regional Hospital; Department Of Medical Oncology
City
Waterford
Country
Ireland
Facility Name
Soroka Medical Center; Hematology Deptartment
City
Beer Sheva
ZIP/Postal Code
8410101
Country
Israel
Facility Name
Bnei-Zion Medical Center; Hematology Dept
City
Haifa
ZIP/Postal Code
3339419
Country
Israel
Facility Name
Hadassah Ein Karem Hospital; Haematology
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Kaplan Medical Center
City
Rehovot
ZIP/Postal Code
7610001
Country
Israel
Facility Name
Ichilov Sourasky Medical Center; Heamatology
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Az. Osp. Pugliese; Divisione de Ematologia
City
Catanzaro
State/Province
Calabria
ZIP/Postal Code
88100
Country
Italy
Facility Name
Ospedale Cardarelli; Divisione Di Ematologia
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Arcispedale S. Anna; Sezione Di Ematologia
City
Ferrara
State/Province
Emilia-Romagna
ZIP/Postal Code
44100
Country
Italy
Facility Name
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
City
Meldola
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
Facility Name
A.O. Universitaria Policlinico Di Modena; Ematologia
City
Modena
State/Province
Emilia-Romagna
ZIP/Postal Code
41100
Country
Italy
Facility Name
AUSL di Piacenza - Ospedale "Guglielmo da Saliceto";U.O. Ematologia
City
Piacenza
State/Province
Emilia-Romagna
ZIP/Postal Code
29121
Country
Italy
Facility Name
Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
City
Ravenna
State/Province
Emilia-Romagna
ZIP/Postal Code
48100
Country
Italy
Facility Name
Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia
City
Rimini
State/Province
Emilia-Romagna
ZIP/Postal Code
47900
Country
Italy
Facility Name
Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
Facility Name
Uni Degli Studi Di Genova; 1A Divisione Di Ematologia
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
Facility Name
Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
City
Novara
State/Province
Piemonte
ZIP/Postal Code
28100
Country
Italy
Facility Name
Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
Azienda ospedaliera oo rr di foggi; Hematology
City
Foggia
State/Province
Puglia
ZIP/Postal Code
71100
Country
Italy
Facility Name
Ospedale Vito Fazzi; Div. Oncoematologia
City
Lecce
State/Province
Puglia
ZIP/Postal Code
73100
Country
Italy
Facility Name
Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09121
Country
Italy
Facility Name
Azienda USL 6 Livorno - P.O. Livorno; U.O. Ematologia Clinica
City
Livorno
State/Province
Toscana
ZIP/Postal Code
57124
Country
Italy
Facility Name
Pusan University Hospital
City
Busan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Samsung Medical Centre; Division of Hematology/Oncology
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
RECUH, Oncology Centre of Latvia; Clinic of Chemotherapy and Heamatology
City
Riga
ZIP/Postal Code
1079
Country
Latvia
Facility Name
Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
City
Kaunas
ZIP/Postal Code
50009
Country
Lithuania
Facility Name
Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Facility Name
Hospital General De Culiacan; Servicio De Hematologia
City
Culiacan
ZIP/Postal Code
80230
Country
Mexico
Facility Name
Hospital General de México; Haematology
City
Mexico City
ZIP/Postal Code
06726
Country
Mexico
Facility Name
Centro Medico Nacional Sxxi - Imss; Haematology
City
Mexico City
ZIP/Postal Code
11270
Country
Mexico
Facility Name
Hospital Universitario Dr. Jose E. Gonzalez; Haematology
City
Monterrey
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Centro de Estudios Clinicos de Queretaro (CECLIQ)
City
Queretaro
ZIP/Postal Code
76000
Country
Mexico
Facility Name
University Clinic of Hematology Skopje, Hospital Care Department
City
Skopje
ZIP/Postal Code
1000
Country
North Macedonia
Facility Name
Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
City
Lublin
ZIP/Postal Code
20-081
Country
Poland
Facility Name
Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
City
Olsztyn
ZIP/Postal Code
10-228
Country
Poland
Facility Name
Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej
City
Opole
ZIP/Postal Code
45-061
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny
City
Slupsk
ZIP/Postal Code
76-200
Country
Poland
Facility Name
Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula
City
Lisboa
ZIP/Postal Code
1600
Country
Portugal
Facility Name
IPO do Porto; Servico de Onco-Hematologia
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Policlinica de Diagnostic Rapid
City
Brasov
ZIP/Postal Code
500152
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta Brasov; Clinica de Hematologie
City
Brasov
ZIP/Postal Code
500326
Country
Romania
Facility Name
Spitalul Clinic Coltea; Clinica de Hematologie
City
Bucuresti
ZIP/Postal Code
030171
Country
Romania
Facility Name
Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
City
Timisoara
ZIP/Postal Code
300079
Country
Romania
Facility Name
FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Vladimirskiy Regional Scientific Research Inst. ; Hematology
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
Facility Name
Almazov Federal Heart, Blood and Endocrinilogy Centre; Hematology department
City
Saint-Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Regional Oncology Center
City
Volgograd
ZIP/Postal Code
400138
Country
Russian Federation
Facility Name
Institute of Hematology
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Fakultna Nemocnica Roosevelta; Dept. of Haematology
City
Banska Bystrica
ZIP/Postal Code
975 17
Country
Slovakia
Facility Name
National Oncology Inst. ; Dept. of Haematology
City
Bratislava
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Hospital Celje; Haematology Dept
City
Celje
ZIP/Postal Code
3000
Country
Slovenia
Facility Name
Clinical Center Ljubljana; Haematology Dept
City
Ljubljana
ZIP/Postal Code
1525
Country
Slovenia
Facility Name
Hospital Maribor; Haematology Dept
City
Maribor
ZIP/Postal Code
2000
Country
Slovenia
Facility Name
Hospital De Txagorritxu; Servicio de Hematologia
City
Vitoria
State/Province
Alava
ZIP/Postal Code
01009
Country
Spain
Facility Name
Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08915
Country
Spain
Facility Name
Hospital Universitario Son Espases
City
Palma De Mallorca
State/Province
Islas Baleares
ZIP/Postal Code
07014
Country
Spain
Facility Name
Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia
City
Logroño
State/Province
LA Rioja
ZIP/Postal Code
26006
Country
Spain
Facility Name
Hospital Quiron de Madrid; Servicio de Hematologia
City
Pozuelo de Alarcon
State/Province
Madrid
ZIP/Postal Code
28223
Country
Spain
Facility Name
Hospital San Pedro De Alcantara; Servicio de Hematologia
City
Caceres
ZIP/Postal Code
10003
Country
Spain
Facility Name
Hospital Universitario Reina Sofia; Servicio de Hematologia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Infanta Leonor; Servicio de Hematologia
City
Madrid
ZIP/Postal Code
28031
Country
Spain
Facility Name
Hospital Universitario Clínico San Carlos; Servicio de Hematología
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Complejo Hospitalario Universitario de Ourense, Servicio de Hematologia
City
Orense
ZIP/Postal Code
32005
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario la Fe; Servicio de Hematologia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Universitetssjukhuset i Linköping, Hematologkliniken
City
Linkoeping
ZIP/Postal Code
581 85
Country
Sweden
Facility Name
Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders
City
Malmö
ZIP/Postal Code
212 24
Country
Sweden
Facility Name
Uddevalla Sjukhus; Medicinkliniken
City
Uddevalla
ZIP/Postal Code
45180
Country
Sweden
Facility Name
Akademiska Sjukhuset
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Kantonsspital Aarau; Zentrum Für Onkologie, Hämatologie & Transfusionsmedizin
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
Universitätsspital Basel; Hämatologie
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana (IOSI)
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Kantonsspital Graubünden;Onkologie und Hämatologie
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
HUG; Hématologie
City
Geneve
ZIP/Postal Code
1211
Country
Switzerland
Facility Name
Luzerner Kantonsspital, Hämatologie
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
Facility Name
OnkoZentrum Zuerich
City
Zürich
ZIP/Postal Code
8038
Country
Switzerland
Facility Name
King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Ramathibodi Hospital; Division of Hematology, Department of Medicine
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Siriraj Hospital; Division of Hematology, Department of Medicine
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Cukurova Uni ; Hematology
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Ankara Numune Egitim Ve Arastirma Hastanesi; Hematoloji Klinigi
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Ankara University; Hematology
City
Ankara
ZIP/Postal Code
06620
Country
Turkey
Facility Name
Pamukkale Uni. Med. Fac.
City
Denizli
ZIP/Postal Code
20070
Country
Turkey
Facility Name
Gaziantep University Medical School; Hematology
City
Gaziantep
ZIP/Postal Code
27310
Country
Turkey
Facility Name
Istanbul Uni Capa Hospital; Hematology
City
Istanbul
ZIP/Postal Code
34390
Country
Turkey
Facility Name
Dokuz Eylul Uni ; Hematology
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Erciyes Uni ; Hematology
City
Kayseri
ZIP/Postal Code
38039
Country
Turkey
Facility Name
Ondokuzmayis University Medical Faculty Heamatology Department
City
Samsun
ZIP/Postal Code
55139
Country
Turkey
Facility Name
Karadeniz Technical Uni School of Medicine; Hematology
City
Trabzon
ZIP/Postal Code
61800
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
33605445
Citation
Stilgenbauer S, Bosch F, Ilhan O, Kisro J, Mahe B, Mikuskova E, Osmanov D, Reda G, Robinson S, Tausch E, Turgut M, Wojtowicz M, Bottcher S, Perretti T, Trask P, Van Hoef M, Leblond V, Foa R. Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: Final analysis of the Phase IIIb GREEN study. Br J Haematol. 2021 Apr;193(2):325-338. doi: 10.1111/bjh.17326. Epub 2021 Feb 19.
Results Reference
derived
PubMed Identifier
31455851
Citation
Bosch F, Cantin G, Cortelezzi A, Knauf W, Tiab M, Turgut M, Zaritskey A, Merot JL, Tausch E, Trunzer K, Robson S, Gresko E, Bottcher S, Foa R, Stilgenbauer S, Leblond V. Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study. Leukemia. 2020 Feb;34(2):441-450. doi: 10.1038/s41375-019-0554-1. Epub 2019 Aug 27.
Results Reference
derived
PubMed Identifier
29749403
Citation
Stilgenbauer S, Leblond V, Foa R, Bottcher S, Ilhan O, Knauf W, Mikuskova E, Renner C, Tausch E, Woszczyk D, Gresko E, Lundberg L, Moore T, Morris T, Robson S, Bosch F. Obinutuzumab plus bendamustine in previously untreated patients with CLL: a subgroup analysis of the GREEN study. Leukemia. 2018 Aug;32(8):1778-1786. doi: 10.1038/s41375-018-0146-5. Epub 2018 Apr 27.
Results Reference
derived

Learn more about this trial

A Safety and Efficacy Study of Obinutuzumab Alone or in Combination With Chemotherapy in Participants With Chronic Lymphocytic Leukemia

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