AzTrials
AzTrials

Chronic Lymphocytic LeukemiaPhase 3NCT01905943

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

A Phase 3 study testing Bendamustine, Chlorambucil and Cyclophosphamide in people with Chronic Lymphocytic Leukemia, run by Hoffmann-La Roche at 174 sites in 31 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Bendamustine, Chlorambucil and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
979 participants
Where
174 sitesin 31 countries
Study dates
4 Nov 2013to 8 Oct 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 19Show fewer
  • 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

Trial locations and contacts

174 sites in 31 countries.

174 sites in 31 countries

France25 sites

  • Hotel Dieu; Medecine D

    Angers, 49933

  • Ch Victor Dupouy; Hematologie

    Argenteuil, 95107

  • Hopital Augustin Morvan; Hematologie

    Brest, 29609

  • Hopital Cote De Nacre; Hematologie Biologique

    Caen, 14033

  • Chu Estaing; Hematologie Clinique Adultes

    Clermont-Ferrand, 63003

  • Hopital Henri Mondor; Hematologie Clinique

    Créteil, 94010

  • Chu Site Du Bocage;Hematologie Clinique

    Dijon, 21079

  • Centre Hospitalier Departemental Les Oudairies

    La Roche-sur-Yon, 85925

  • Ch Du Mans; Medecine Hematologie Oncologie

    Le Mans, 72037

  • Hopital Claude Huriez; Hematologie

    Lille, 59037

  • Hopital Uni Ire Dupuytren; Hematologie

    Limoges, 87042

  • Hopital Saint Eloi; Hematologie Oncologie Medicale

    Montpellier, 34295

  • Hopital Emile Muller; Hematologie

    Mulhouse, 68070

  • Hopital Hotel Dieu Et Hme;Hopital De Jour

    Nantes, 44093

  • Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

    Paris, 75475

  • Hopital Saint Antoine; Hematologie Clinique

    Paris, 75571

  • Hopital Pitie Salpetriere; Hematologie Clinique

    Paris, 75651

  • Hopital Saint Jean; Hematologie

    Perpignan, 66046

  • Hopital De Haut Leveque; Hematologie Clinique

    Pessac, 33604

  • Ch Lyon Sud; Hemato Secteur Jules Courmont

    Pierre-Bénite, 69495

  • Centre Hospitalier René Dubos; Hematologie

    Pontoise, 95300

  • Hopital Robert Debre; Hematologie Clinique

    Reims, 51092

  • Centre Henri Becquerel; Hematologie

    Rouen, 76038

  • Centre Hospitalier de Saint Brieuc - Hôpital Yves Le Foll

    Saint-Brieuc, 22027

  • Hopital Bretonneau; Hematologie Therapie Cellulaire

    Tours, 37044

Other trials in France

Italy18 sites

  • Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.

    Cagliari, Sardinia, 09121

  • Az. Osp. Pugliese; Divisione de Ematologia

    Catanzaro, Calabria, 88100

  • Arcispedale S. Anna; Sezione Di Ematologia

    Ferrara, Emilia-Romagna, 44100

  • Azienda ospedaliera oo rr di foggi; Hematology

    Foggia, Apulia, 71100

  • Uni Degli Studi Di Genova; 1A Divisione Di Ematologia

    Genoa, Liguria, 16132

  • Ospedale Vito Fazzi; Div. Oncoematologia

    Lecce, Apulia, 73100

  • Azienda USL 6 Livorno - P.O. Livorno; U.O. Ematologia Clinica

    Livorno, Tuscany, 57124

  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

    Meldola, Emilia-Romagna, 47014

  • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora

    Milan, Lombardy, 20122

  • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia

    Milan, Lombardy, 20162

  • A.O. Universitaria Policlinico Di Modena; Ematologia

    Modena, Emilia-Romagna, 41100

  • Ospedale Cardarelli; Divisione Di Ematologia

    Naples, Campania, 80131

  • Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad

    Novara, Piedmont, 28100

  • AUSL di Piacenza - Ospedale "Guglielmo da Saliceto";U.O. Ematologia

    Piacenza, Emilia-Romagna, 29121

  • Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia

    Ravenna, Emilia-Romagna, 48100

  • Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia

    Rimini, Emilia-Romagna, 47900

  • Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol

    Rome, Lazio, 00161

  • Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I

    Turin, Piedmont, 10126

Other trials in Italy

Germany16 sites

  • Hämatologisch-onkologische Praxis Dr. med. - Heinrich, - Bangerter

    Augsburg, 86150

  • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie

    Dresden, 01307

  • Onkologisches Zentrum am Bethanien-Kankenhaus

    Frankfurt, 60389

  • Gemeinschaftspraxis; Prof. Dr. Michael Kiehl und Dr.med. Wolfgang Stein

    Frankfurt (Oder), 15236

  • Dres.Andreas Ammon und Dirk Meyer

    Göttingen, 37073

  • OncoResearch Lerchenfeld GmbH

    Hamburg, 22081

  • Onkologische Schwerpunktpraxis Lübeck

    Lübeck, 23562

  • Onkologische Gemeinschaftspraxis

    Magdeburg, 39104

  • Dres. Hans-Dieter Schick Dorothea Schick Burkhard Schmidt u.w.

    München, 81241

  • Kliniken Ostalb, Stauferklinikum Schwäbisch-Gmünd; Zentrum für Innere Medizin

    Mutlangen, 73557

  • Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura

    Neunkirchen/Saar, 66538

  • eps - early phase GmbH

    Pößneck, 07381

  • Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie

    Recklinghausen, 45659

  • Schwerpunktpraxis & Tagesklinik f. Hämatologie & Onkologie Regensdorf / Schwandorf / Wörth

    Regensburg, 93053

  • Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.

    Ulm, 89081

  • Onkologische Schwerpunktpraxis Dres. Rudolf Schlag und Björn Schöttker

    Würzburg, 97080

Other trials in Germany

Spain12 sites

  • Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia

    Badalona, Barcelona, 08915

  • Hospital San Pedro De Alcantara; Servicio de Hematologia

    Cáceres, 10003

  • Hospital Universitario Reina Sofia; Servicio de Hematologia

    Córdoba, 14004

  • Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia

    Logroño, La Rioja, 26006

  • Hospital Infanta Leonor; Servicio de Hematologia

    Madrid, 28031

  • Hospital Universitario Clínico San Carlos; Servicio de Hematología

    Madrid, 28040

  • Complejo Hospitalario Universitario de Ourense, Servicio de Hematologia

    Ourense, 32005

  • Hospital Universitario Son Espases

    Palma de Mallorca, Balearic Islands, 07014

  • Hospital Quiron de Madrid; Servicio de Hematologia

    Pozuelo de Alarcón, Madrid, 28223

  • Hospital Universitario Virgen del Rocio; Servicio de Hematologia

    Seville, 41013

  • Hospital Universitario la Fe; Servicio de Hematologia

    Valencia, 46026

  • Hospital De Txagorritxu; Servicio de Hematologia

    Vitoria-Gasteiz, Alava, 01009

Other trials in Spain

Turkey (Türkiye)10 sites

  • Cukurova Uni ; Hematology

    Adana, 01330

  • Ankara Numune Egitim Ve Arastirma Hastanesi; Hematoloji Klinigi

    Ankara, 06100

  • Ankara University; Hematology

    Ankara, 06620

  • Pamukkale Uni. Med. Fac.

    Denizli, 20070

  • Gaziantep University Medical School; Hematology

    Gaziantep, 27310

  • Istanbul Uni Capa Hospital; Hematology

    Istanbul, 34390

  • Dokuz Eylul Uni ; Hematology

    Izmir, 35100

  • Erciyes Uni ; Hematology

    Kayseri, 38039

  • Ondokuzmayis University Medical Faculty Heamatology Department

    Samsun, 55139

  • Karadeniz Technical Uni School of Medicine; Hematology

    Trabzon, 61800

Other trials in Turkey (Türkiye)

Canada9 sites

  • Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials

    Barrie, Ontario, L4M 6M2

  • Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie

    Greenfield Park, Quebec, J4V 2H1

  • Queen Elizabeth II Health Sciences Centre; Oncology

    Halifax, Nova Scotia, B3H 2Y9

  • Regional health authority A vitalite health network

    Moncton, New Brunswick, E1C 8X3

  • Hopital Maisonneuve- Rosemont; Oncology

    Montreal, Quebec, H1T 2M4

  • CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie

    Québec, G1J 1Z4

  • Centre de sante et de services sociaux Rimouski Neigette

    Rimouski, Quebec, G5L 5T1

  • Saskatoon Cancer Centre; Uni of Saskatoon Campus

    Saskatoon, Saskatchewan, S7N 4H4

  • Cancer Care Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Brazil8 sites

  • Hospital de Cancer de Barretos

    Barretos, São Paulo, 14784-400

  • Hospital Amaral Carvalho

    Jaú, São Paulo, 17210-120

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Instituto de Ensino e Pesquisa Sao Lucas - IEP

    São Paulo, São Paulo, 01236-030

  • Hospital Sirio Libanes; Centro de Oncologia

    São Paulo, São Paulo, 01308-050

  • Hospital Estadual do Servidor Publico; Hematologia

    São Paulo, São Paulo, 04029-000

  • Hospital das Clinicas - FMUSP; Hematologia

    São Paulo, São Paulo, 05403-000

  • Hospital Santa Marcelina;Oncologia

    São Paulo, São Paulo, 08270-070

Other trials in Brazil

Switzerland7 sites

  • Kantonsspital Aarau; Zentrum Für Onkologie, Hämatologie & Transfusionsmedizin

    Aarau, 5001

  • Universitätsspital Basel; Hämatologie

    Basel, 4031

  • Istituto Oncologico della Svizzera Italiana (IOSI)

    Bellinzona, 6500

  • Kantonsspital Graubünden;Onkologie und Hämatologie

    Chur, 7000

  • HUG; Hématologie

    Geneva, 1211

  • Luzerner Kantonsspital, Hämatologie

    Lucerne, 6000

  • OnkoZentrum Zuerich

    Zurich, 8038

Other trials in Switzerland

Belgium5 sites

  • Hospital Erasme; Neurologie

    Brussels, 1070

  • Cliniques Universitaires St-Luc

    Brussels, 1200

  • Jessa Zkh (Campus Virga Jesse)

    Hasselt, 3500

  • CHU Sart-Tilman

    Liège, 4000

  • Sint Augustinus Wilrijk

    Wilrijk, 2610

Other trials in Belgium

Greece5 sites

  • General Hospital of Athens Evangelismos; Hematology

    Athens, 106 76

  • Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine

    Athens, 115 27

  • Laiko General Hospital; Hematology Clinic

    Athens, 115 27

  • University Hospital of Ioannina; Hematology

    Ioannina, 455 00

  • Georgios Papanikolaou Hospital; Hematology Department

    Thessaloniki, 570 10

Other trials in Greece

Israel5 sites

  • Soroka Medical Center; Hematology Deptartment

    Beersheba, 8410101

  • Bnei-Zion Medical Center; Hematology Dept

    Haifa, 3339419

  • Hadassah Ein Karem Hospital; Haematology

    Jerusalem, 9112001

  • Kaplan Medical Center

    Rehovot, 7610001

  • Ichilov Sourasky Medical Center; Heamatology

    Tel Aviv, 6423906

Other trials in Israel

Mexico5 sites

  • Hospital General De Culiacan; Servicio De Hematologia

    Culiacán, 80230

  • Hospital General de México; Haematology

    Mexico City, 06726

  • Centro Medico Nacional Sxxi - Imss; Haematology

    Mexico City, 11270

  • Hospital Universitario Dr. Jose E. Gonzalez; Haematology

    Monterrey, 64460

  • Centro de Estudios Clinicos de Queretaro (CECLIQ)

    Querétaro, 76000

Other trials in Mexico

Thailand5 sites

  • King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine

    Bangkok, 10330

  • Ramathibodi Hospital; Division of Hematology, Department of Medicine

    Bangkok, 10400

  • Siriraj Hospital; Division of Hematology, Department of Medicine

    Bangkok, 10700

  • Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine

    Chiang Mai, 50200

  • Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine

    Khon Kaen, 40002

Other trials in Thailand

Poland4 sites

  • Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie

    Lublin, 20-081

  • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

    Olsztyn, 10-228

  • Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej

    Opole, 45-061

  • Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny

    Słupsk, 76-200

Other trials in Poland

Romania4 sites

  • Policlinica de Diagnostic Rapid

    Brasov, 500152

  • Spitalul Clinic Judetean de Urgenta Brasov; Clinica de Hematologie

    Brasov, 500326

  • Spitalul Clinic Coltea; Clinica de Hematologie

    Bucharest, 030171

  • Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie

    Timișoara, 300079

Other trials in Romania

Russia4 sites

  • FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF

    Moscow, 115478

  • Vladimirskiy Regional Scientific Research Inst. ; Hematology

    Moscow, 129110

  • Almazov Federal Heart, Blood and Endocrinilogy Centre; Hematology department

    Saint Petersburg, 197341

  • Regional Oncology Center

    Volgograd, 400138

Other trials in Russia

Sweden4 sites

  • Universitetssjukhuset i Linköping, Hematologkliniken

    Linköping, 581 85

  • Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders

    Malmö, 212 24

  • Uddevalla Sjukhus; Medicinkliniken

    Uddevalla, 45180

  • Akademiska Sjukhuset

    Uppsala, 751 85

Other trials in Sweden

Finland3 sites

  • Kuopio University Hospital

    Kuopio, 70211

  • Tampere University Hospital; Hematology

    Tampere, 33521

  • Turku Uni Central Hospital; Dept of Internal Medicine

    Turku, 20520

Other trials in Finland

Ireland3 sites

  • Mater Misericordiae Uni Hospital; Oncology

    Dublin, 7

  • University Hospital Limerick - Oncology

    Limerick

  • Waterford Regional Hospital; Department Of Medical Oncology

    Waterford

Other trials in Ireland

Slovenia3 sites

  • Hospital Celje; Haematology Dept

    Celje, 3000

  • Clinical Center Ljubljana; Haematology Dept

    Ljubljana, 1525

  • Hospital Maribor; Haematology Dept

    Maribor, 2000

Other trials in Slovenia

South Korea3 sites

  • Pusan University Hospital

    Busan, 602-739

  • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

    Seoul, 03080

  • Samsung Medical Centre; Division of Hematology/Oncology

    Seoul, 135-710

Other trials in South Korea

Bosnia and Herzegovina2 sites

  • University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept

    Banja Luka, 88000

  • University Clinical Center Sarajevo, Clinic for Hematology

    Sarajevo, 71000

Other trials in Bosnia and Herzegovina

Egypt2 sites

  • Cairo University Hospital Al Kasr El Ainy

    Cairo, 11559

  • National Cancer Institute

    Cairo, 11796

Other trials in Egypt

Estonia2 sites

  • North Estonia Regional Hospital; Hematology

    Tallinn, 13419

  • Tartu Uni Hospital; Hematology - Oncology Clinic

    Tartu, 51014

Other trials in Estonia

Lithuania2 sites

  • Hospital of Lithuanian University of Health. Sciences Kaunas Clinics

    Kaunas, 50009

  • Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center

    Vilnius, 08661

Other trials in Lithuania

Portugal2 sites

  • Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula

    Lisbon, 1600

  • IPO do Porto; Servico de Onco-Hematologia

    Porto, 4200-072

Other trials in Portugal

Slovakia2 sites

  • Fakultna Nemocnica Roosevelta; Dept. of Haematology

    Banská Bystrica, 975 17

  • National Oncology Inst. ; Dept. of Haematology

    Bratislava, 833 10

Other trials in Slovakia

Argentina1 site

  • Hospital Iturraspe

    Santa Fe, 3000

Other trials in Argentina

Latvia1 site

  • RECUH, Oncology Centre of Latvia; Clinic of Chemotherapy and Heamatology

    Riga, 1079

Other trials in Latvia

North Macedonia1 site

  • University Clinic of Hematology Skopje, Hospital Care Department

    Skopje, 1000

Other trials in North Macedonia

Serbia1 site

  • Institute of Hematology

    Belgrade, 11000

Other trials in Serbia

About this study

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

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.

Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BendamustineDrug

    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).

  • ChlorambucilDrug

    Chlorambucil 0.5 mg/kg p.o. qd on Day 1 and Day 15 in non-fit participants only.

  • CyclophosphamideDrug

    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.

  • FludarabineDrug

    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.

  • ObinutuzumabDrug

    Also called Gazyva®, RO5072759

    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.

Study groups in NCT01905943
Study groupRoleWhat they receive
ObinutuzumabExperimentalParticipants 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.
Receives: Drug: Bendamustine; Drug: Chlorambucil; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Baseline up to time of primary completion (3 years)

  2. 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.

    Measured: Baseline up to time of primary completion (3 years)

  3. 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.

    Measured: Baseline up to time of primary completion (3 years)

Secondary outcomes (9)

  1. 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.

    Measured: 3 months after the last dose of study treatment (up to approximately 5 years)

  2. 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).

    Measured: 3 months after the last dose of study treatment (up to approximately 5 years)

  3. 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.

    Measured: 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)

  4. 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.

    Measured: 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)

  5. 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.

    Measured: 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)

  6. 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.

    Measured: 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)

  7. 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.

    Measured: Baseline until death (Approximately up to 5 years)

  8. 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.

    Measured: Baseline until end of study (up to approximately 5 years)

  9. 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.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jul 2013 (estimated)
  2. Study start4 Nov 2013
  3. Primary completion29 Dec 2016
  4. Study completion8 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
979 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01905943
Sponsor's protocol ID
MO28543
Other IDs
2013-000087-29
Status last verified
Oct 2019
First submitted
19 Jul 2013
Last updated
28 Oct 2019
FDA-regulated drug
Yes
FDA-regulated device
No

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.

    PubMed 33605445

  • 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.

    PubMed 31455851

  • 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.

    PubMed 29749403

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bendamustine, Chlorambucil and Cyclophosphamide in people with Chronic Lymphocytic Leukemia, run by Hoffmann-La Roche at 174 sites in 31 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 174 sites in France, Italy, Germany, Spain, Turkey (Türkiye) and 26 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) (time frame: Baseline up to time of primary completion (3 years)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01905943, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2019.

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