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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Bendamustine; Drug: Chlorambucil; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Obinutuzumab

• Study Type: Interventional
• Enrollment (Actual): 979
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Santa Fé, Argentina, 3000
    • Hospital Iturraspe
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Bruxelles, Belgium, 1070
    • Hospital Erasme; Neurologie
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 88000
    • University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinical Center Sarajevo, Clinic for Hematology
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • Jau, SP, Brazil, 17210-120
      • Hospital Amaral Carvalho
    • Sao Paulo, SP, Brazil, 01308-050
      • Hospital Sirio Libanes; Centro de Oncologia
    • Sao Paulo, SP, Brazil, 04029-000
      • Hospital Estadual do Servidor Publico; Hematologia
    • Sao Paulo, SP, Brazil, 01236-030
      • Instituto de Ensino e Pesquisa Sao Lucas - IEP
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP; Hematologia
    • Sao Paulo, SP, Brazil, 08270-070
      • Hospital Santa Marcelina;Oncologia
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Regional health authority A vitalite health network
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre; Oncology
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve- Rosemont; Oncology
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre De Sante Et De Services Sociaux Rimouski Neigette
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre; Uni of Saskatoon Campus
• Egypt
  • Cairo, Egypt, 11796
    • National Cancer Institute
  • Cairo, Egypt, 11559
    • Cairo University Hospital Al Kasr El Ainy
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Regional Hospital; Hematology
  • Tartu, Estonia, 51014
    • Tartu Uni Hospital; Hematology - Oncology Clinic
• Finland
  • Kuopio, Finland, 70211
    • Kuopio University Hospital
  • Tampere, Finland, 33521
    • Tampere University Hospital; Hematology
  • Turku, Finland, 20520
    • Turku Uni Central Hospital; Dept of Internal Medicine
• France
  • Angers, France, 49933
    • Hotel Dieu; Medecine D
  • Argenteuil, France, 95107
    • Ch Victor Dupouy; Hematologie
  • Brest, France, 29609
    • Hopital Augustin Morvan; Hematologie
  • Caen, France, 14033
    • Hopital Cote De Nacre; Hematologie Biologique
  • Clermont Ferrand, France, 63003
    • Chu Estaing; Hematologie Clinique Adultes
  • Creteil, France, 94010
    • Hopital Henri Mondor; Hematologie Clinique
  • Dijon, France, 21079
    • Chu Site Du Bocage;Hematologie Clinique
  • La Roche Sur Yon, France, 85925
    • Centre Hospitalier Départemental Les Oudairies
  • Le Mans, France, 72037
    • Ch Du Mans; Medecine Hematologie Oncologie
  • Lille, France, 59037
    • Hopital Claude Huriez; Hematologie
  • Limoges, France, 87042
    • Hopital Uni Ire Dupuytren; Hematologie
  • Montpellier, France, 34295
    • Hopital Saint Eloi; Hematologie Oncologie Medicale
  • Mulhouse, France, 68070
    • Hopital Emile Muller; Hematologie
  • Nantes, France, 44093
    • Hopital Hotel Dieu Et Hme;Hopital De Jour
  • Paris, France, 75475
    • Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
  • Paris, France, 75651
    • Hopital Pitie Salpetriere; Hematologie Clinique
  • Paris, France, 75571
    • Hopital Saint Antoine; Hematologie Clinique
  • Perpignan, France, 66046
    • Hopital Saint Jean; Hematologie
  • Pessac, France, 33604
    • Hopital De Haut Leveque; Hematologie Clinique
  • Pierre Benite, France, 69495
    • Ch Lyon Sud; Hemato Secteur Jules Courmont
  • Pontoise, France, 95300
    • Centre Hospitalier René Dubos; Hematologie
  • Reims, France, 51092
    • Hopital Robert Debre; Hematologie Clinique
  • Rouen, France, 76038
    • Centre Henri Becquerel; Hematologie
  • St Brieuc, France, 22027
    • Centre Hospitalier de Saint Brieuc - Hôpital Yves Le Foll
  • Tours, France, 37044
    • Hopital Bretonneau; Hematologie Therapie Cellulaire
• Germany
  • Augsburg, Germany, 86150
    • Hämatologisch-onkologische Praxis Dr. med. - Heinrich, - Bangerter
  • Dresden, Germany, 01307
    • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
  • Frankfurt, Germany, 60389
    • Onkologisches Zentrum am Bethanien-Kankenhaus
  • Frankfurt an der Oder, Germany, 15236
    • Gemeinschaftspraxis; Prof. Dr. Michael Kiehl und Dr.med. Wolfgang Stein
  • Göttingen, Germany, 37073
    • Dres.Andreas Ammon und Dirk Meyer
  • Hamburg, Germany, 22081
    • OncoResearch Lerchenfeld GmbH
  • Lübeck, Germany, 23562
    • Onkologische Schwerpunktpraxis Lübeck
  • Magdeburg, Germany, 39104
    • Onkologische Gemeinschaftspraxis
  • Mutlangen, Germany, 73557
    • Kliniken Ostalb, Stauferklinikum Schwäbisch-Gmünd; Zentrum für Innere Medizin
  • München, Germany, 81241
    • Dres. Hans-Dieter Schick Dorothea Schick Burkhard Schmidt u.w.
  • Neunkirchen/Saar, Germany, 66538
    • Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura
  • Pößneck, Germany, 07381
    • eps - early phase GmbH
  • Recklinghausen, Germany, 45659
    • Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie
  • Regensburg, Germany, 93053
    • Schwerpunktpraxis & Tagesklinik f. Hämatologie & Onkologie Regensdorf / Schwandorf / Wörth
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
  • Würzburg, Germany, 97080
    • Onkologische Schwerpunktpraxis Dres. Rudolf Schlag und Björn Schöttker
• Greece
  • Athens, Greece, 106 76
    • General Hospital of Athens Evangelismos; Hematology
  • Athens, Greece, 115 27
    • Laiko General Hospital; Hematology Clinic
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine
  • Ioannina, Greece, 455 00
    • University Hospital of Ioannina; Hematology
  • Thessaloniki, Greece, 570 10
    • Georgios Papanikolaou Hospital; Hematology Department
• Ireland
  • Dublin, Ireland, 7
    • Mater Misericordiae Uni Hospital; Oncology
  • Limerick, Ireland
    • University Hospital Limerick - Oncology
  • Waterford, Ireland
    • Waterford Regional Hospital; Department Of Medical Oncology
• Israel
  • Beer Sheva, Israel, 8410101
    • Soroka Medical Center; Hematology Deptartment
  • Haifa, Israel, 3339419
    • Bnei-Zion Medical Center; Hematology Dept
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hospital; Haematology
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Ichilov Sourasky Medical Center; Heamatology
• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Az. Osp. Pugliese; Divisione de Ematologia
  • Campania
    • Napoli, Campania, Italy, 80131
      • Ospedale Cardarelli; Divisione Di Ematologia
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44100
      • Arcispedale S. Anna; Sezione Di Ematologia
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena; Ematologia
    • Piacenza, Emilia-Romagna, Italy, 29121
      • AUSL di Piacenza - Ospedale "Guglielmo da Saliceto";U.O. Ematologia
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
    • Rimini, Emilia-Romagna, Italy, 47900
      • Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Uni Degli Studi Di Genova; 1A Divisione Di Ematologia
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
    • Milano, Lombardia, Italy, 20162
      • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
  • Piemonte
    • Novara, Piemonte, Italy, 28100
      • Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
    • Torino, Piemonte, Italy, 10126
      • Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I
  • Puglia
    • Foggia, Puglia, Italy, 71100
      • Azienda ospedaliera oo rr di foggi; Hematology
    • Lecce, Puglia, Italy, 73100
      • Ospedale Vito Fazzi; Div. Oncoematologia
  • Sardegna
    • Cagliari, Sardegna, Italy, 09121
      • Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.
  • Toscana
    • Livorno, Toscana, Italy, 57124
      • Azienda USL 6 Livorno - P.O. Livorno; U.O. Ematologia Clinica
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Centre; Division of Hematology/Oncology
• Latvia
  • Riga, Latvia, 1079
    • RECUH, Oncology Centre of Latvia; Clinic of Chemotherapy and Heamatology
• Lithuania
  • Kaunas, Lithuania, 50009
    • Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center
• Mexico
  • Culiacan, Mexico, 80230
    • Hospital General De Culiacan; Servicio De Hematologia
  • Mexico City, Mexico, 06726
    • Hospital General de México; Haematology
  • Mexico City, Mexico, 11270
    • Centro Medico Nacional Sxxi - Imss; Haematology
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr. Jose E. Gonzalez; Haematology
  • Queretaro, Mexico, 76000
    • Centro de Estudios Clínicos de Querétaro (CECLIQ)
• North Macedonia
  • Skopje, North Macedonia, 1000
    • University Clinic of Hematology Skopje, Hospital Care Department
• Poland
  • Lublin, Poland, 20-081
    • Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
  • Olsztyn, Poland, 10-228
    • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
  • Opole, Poland, 45-061
    • Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej
  • Slupsk, Poland, 76-200
    • Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny
• Portugal
  • Lisboa, Portugal, 1600
    • Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Onco-Hematologia
• Romania
  • Brasov, Romania, 500152
    • Policlinica de Diagnostic Rapid
  • Brasov, Romania, 500326
    • Spitalul Clinic Judetean de Urgenta Brasov; Clinica de Hematologie
  • Bucuresti, Romania, 030171
    • Spitalul Clinic Coltea; Clinica de Hematologie
  • Timisoara, Romania, 300079
    • Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
• Russian Federation
  • Moscow, Russian Federation, 115478
    • FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
  • Moscow, Russian Federation, 129110
    • Vladimirskiy Regional Scientific Research Inst. ; Hematology
  • Saint-Petersburg, Russian Federation, 197341
    • Almazov Federal Heart, Blood and Endocrinilogy Centre; Hematology department
  • Volgograd, Russian Federation, 400138
    • Regional Oncology Center
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Hematology
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna Nemocnica Roosevelta; Dept. of Haematology
  • Bratislava, Slovakia, 833 10
    • National Oncology Inst. ; Dept. of Haematology
• Slovenia
  • Celje, Slovenia, 3000
    • Hospital Celje; Haematology Dept
  • Ljubljana, Slovenia, 1525
    • Clinical Center Ljubljana; Haematology Dept
  • Maribor, Slovenia, 2000
    • Hospital Maribor; Haematology Dept
• Spain
  • Caceres, Spain, 10003
    • Hospital San Pedro de Alcantara; Servicio de Hematología
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia; Servicio de Hematologia
  • Madrid, Spain, 28031
    • Hospital Infanta Leonor; Servicio de Hematologia
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Hematología
  • Orense, Spain, 32005
    • Complejo Hospitalario Universitario de Ourense, Servicio de Hematologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Hematologia
  • Valencia, Spain, 46026
    • Hospital Universitario la Fe; Servicio de Hematologia
  • Alava
    • Vitoria, Alava, Spain, 01009
      • Hospital De Txagorritxu; Servicio de Hematologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
      • Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07014
      • Hospital Universitario Son Espases
  • LA Rioja
    • Logroño, LA Rioja, Spain, 26006
      • Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Hematologia
• Sweden
  • Linkoeping, Sweden, 581 85
    • Universitetssjukhuset i Linköping, Hematologkliniken
  • Malmö, Sweden, 212 24
    • Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders
  • Uddevalla, Sweden, 45180
    • Uddevalla Sjukhus; Medicinkliniken
  • Uppsala, Sweden, 751 85
    • Akademiska Sjukhuset
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau; Zentrum Für Onkologie, Hämatologie & Transfusionsmedizin
  • Basel, Switzerland, 4031
    • Universitätsspital Basel; Hämatologie
  • Bellinzona, Switzerland, 6500
    • Istituto Oncologico della Svizzera Italiana (IOSI)
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden;Onkologie und Hämatologie
  • Geneve, Switzerland, 1211
    • HUG; Hématologie
  • Luzern, Switzerland, 6000
    • Luzerner Kantonsspital, Hämatologie
  • Zürich, Switzerland, 8038
    • OnkoZentrum Zuerich
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Division of Hematology, Department of Medicine
  • Bangkok, Thailand, 10700
    • Siriraj Hospital; Division of Hematology, Department of Medicine
  • Chiang Mai, Thailand, 50200
    • Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine
• Turkey
  • Adana, Turkey, 01330
    • Cukurova Uni ; Hematology
  • Ankara, Turkey, 06100
    • Ankara Numune Egitim Ve Arastirma Hastanesi; Hematoloji Klinigi
  • Ankara, Turkey, 06620
    • Ankara University; Hematology
  • Denizli, Turkey, 20070
    • Pamukkale Uni. Med. Fac.
  • Gaziantep, Turkey, 27310
    • Gaziantep University Medical School; Hematology
  • Istanbul, Turkey, 34390
    • Istanbul Uni Capa Hospital; Hematology
  • Izmir, Turkey, 35100
    • Dokuz Eylul Uni ; Hematology
  • Kayseri, Turkey, 38039
    • Erciyes Uni ; Hematology
  • Samsun, Turkey, 55139
    • Ondokuzmayis University Medical Faculty Heamatology Department
  • Trabzon, Turkey, 61800
    • Karadeniz Technical Uni School of Medicine; Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Obinutuzumab; 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.

Drug: Bendamustine; 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).; Drug: Chlorambucil; Chlorambucil 0.5 mg/kg p.o. qd on Day 1 and Day 15 in non-fit participants only.; Drug: Cyclophosphamide; 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.; Drug: Fludarabine; 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.; Drug: Obinutuzumab; 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.; Other Names: Gazyva®, RO5072759

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline up to time of primary completion (3 years)
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.	Baseline up to time of primary completion (3 years)
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.	Baseline up to time of primary completion (3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 months after the last dose of study treatment (up to approximately 5 years)
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).	3 months after the last dose of study treatment (up to approximately 5 years)
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.	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)
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.	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)
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.	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)
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.	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)
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.	Baseline until death (Approximately up to 5 years)
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.	Baseline until end of study (up to approximately 5 years)
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.	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2013
• Primary Completion (Actual): December 29, 2016
• Study Completion (Actual): October 8, 2018

Study Registration Dates

• First Submitted: July 19, 2013
• First Submitted That Met QC Criteria: July 19, 2013
• First Posted (Estimate): July 23, 2013

Study Record Updates

• Last Update Posted (Actual): October 28, 2019
• Last Update Submitted That Met QC Criteria: October 24, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Bendamustine Hydrochloride; Fludarabine; Obinutuzumab; Chlorambucil
• Other Study ID Numbers: MO28543; 2013-000087-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No