Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia
NCT ID: NCT02242942
Last Updated: 2025-11-06
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
445 participants
INTERVENTIONAL
2014-12-31
2025-08-27
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Safety Run-in Obinutuzumab + Venetoclax
Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.
Venetoclax
Venetoclax, oral tablet: 20 mg daily during Cycle 1, Day 22-28; 50 mg daily during Cycle 2, Day 1-7; 100 mg daily during Cycle 2, Day 8-14; 200 mg daily during Cycle 2, Day 15-21; 400 mg daily during Cycle 2, Day 22-28 and on Day 1-28 for all subsequent cycles until the end of Cycle 12.
Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Obinutuzumab + Chlorambucil
Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.
Chlorambucil
Chlorambucil 0.5 milligrams per kilogram (mg/kg) orally at Day 1 and Day 15 at of each 28 day cycle for 12 cycles.
Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Obinutuzumab + Venetoclax
Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Venetoclax
Venetoclax, oral tablet: 20 mg daily during Cycle 1, Day 22-28; 50 mg daily during Cycle 2, Day 1-7; 100 mg daily during Cycle 2, Day 8-14; 200 mg daily during Cycle 2, Day 15-21; 400 mg daily during Cycle 2, Day 22-28 and on Day 1-28 for all subsequent cycles until the end of Cycle 12.
Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Interventions
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Chlorambucil
Chlorambucil 0.5 milligrams per kilogram (mg/kg) orally at Day 1 and Day 15 at of each 28 day cycle for 12 cycles.
Venetoclax
Venetoclax, oral tablet: 20 mg daily during Cycle 1, Day 22-28; 50 mg daily during Cycle 2, Day 1-7; 100 mg daily during Cycle 2, Day 8-14; 200 mg daily during Cycle 2, Day 15-21; 400 mg daily during Cycle 2, Day 22-28 and on Day 1-28 for all subsequent cycles until the end of Cycle 12.
Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* CLL requiring treatment according to IWCLL criteria
* Total Cumulative Illness Rating Scale (CIRS score) greater than (\>) 6
* Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL
* Adequate liver function
* Life expectancy \> 6 months
* Agreement to use highly effective contraceptive methods per protocol
Exclusion Criteria
* Known central nervous system involvement
* Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
* An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
* Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
* Inadequate renal function
* History of prior malignancy, except for conditions as listed in the protocol if participants have recovered from the acute side effects incurred as a result of previous therapy
* Use of investigational agents or concurrent anti-cancer treatment within the last 4 weeks of registration
* Participants with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
* Hypersensitivity to chlorambucil, obinutuzumab, or venetoclax or to any of the excipients
* Pregnant women and nursing mothers
* Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology) or positive test result for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing)
* Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)
* Requires the use of warfarin, marcumar, or phenprocoumon
* Received agents known to be strong and moderate Cytochrome P450 3A inhibitors or inducers within 7 days prior to the first dose of study drug
18 Years
ALL
No
Sponsors
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AbbVie
INDUSTRY
German CLL Study Group
OTHER
Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
City of Hope
Duarte, California, United States
UC San Diego Health System
La Jolla, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
Winship Cancer Institute
Atlanta, Georgia, United States
Ingalls Memorial Hospital
Harvey, Illinois, United States
Henry Ford Hospital
Detroit, Michigan, United States
Joe Arrington Cancer Center
Lubbock, Texas, United States
Hospital Italiano
Buenos Aires, , Argentina
Liverpool Hospital
Liverpool BC, New South Wales, Australia
Tweed Hospital
Tweed Heads, New South Wales, Australia
The Townsville Hospital
Douglas, Queensland, Australia
Princess Alexandra Hospital Woolloongabba
Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Ashford Cancer Centre Research
Ashford, South Australia, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
The Northern Hospital
Epping, Victoria, Australia
Monash Medical Centre
Melbourne, Victoria, Australia
Tiroler Landeskrankenanstalten Ges.M.B.H.
Innsbruck, , Austria
Medizinische Universität Wien
Vienna, , Austria
Hanusch-Krankenhaus
Vienna, , Austria
Hospital das Clinicas - UFRGS
Porto Alegre, Rio Grande do Sul, Brazil
Instituto de Ensino e Pesquisa Sao Lucas - IEP
São Paulo, São Paulo, Brazil
Hospital Sírio-Libanês
São Paulo, São Paulo, Brazil
Hospital das Clinicas - FMUSP
São Paulo, São Paulo, Brazil
UMHAT Dr Georgi Stranski
Pleven, , Bulgaria
UMHAT " Sveti Georgi" Plovdiv - Clinic of Oncology and Hematology
Plovdiv, , Bulgaria
University Hospital Sv.Georgi Clnic of Hematology
Plovdiv, , Bulgaria
University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD
Sofia, , Bulgaria
MHAT Hristo Botev
Vratsa, , Bulgaria
Arthur J.E. Child Comprehensive Cancer Center
Calgary, Alberta, Canada
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada
Jewish General Hospital
Montreal, Quebec, Canada
University Hospital Center Zagreb
Zagreb, , Croatia
University Hospital Merkur Clinic for Internal Medicine/ Hematology
Zagreb, , Croatia
Herlev Hospital
Herlev, , Denmark
Rigshospitalet
København Ø, , Denmark
Sjaellands Universitetshospital, Roskilde
Roskilde, , Denmark
Sygehus Lillebælt, Vejle
Vejle, , Denmark
North Estonia medical Centre
Tallinn, , Estonia
Tartu Uni Hospital
Tartu, , Estonia
Institut d'Hématologie de Basse Normandie
Caen, , France
Hopital Henri Mondor
Créteil, , France
CHU de Grenoble
Grenoble, , France
Centre Jean Bernard
Le Mans, , France
Centre Leon Berard
Lyon, , France
Hôpital Saint Eloi
Montpellier, , France
Hopital Hotel Dieu Et Hme
Nantes, , France
Hopital Saint Louis
Paris, , France
Hopital Pontchaillou
Rennes, , France
Centre Henri Becquerel
Rouen, , France
CH de Toulon Hôpital Sainte Musse
Toulon, , France
Institut Gustave Roussy - Hematologie
Villejuif, , France
Uniklinik RWTH Aachen
Aachen, , Germany
Charite - Campus Virchow-Klinikum
Berlin, , Germany
Charite - Universitätsmedizin Berlin
Berlin, , Germany
Universitätsklinikum Köln
Cologne, , Germany
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf
Dresden, , Germany
Uniklinikum "Carl Gustav Carus";Med. Klinik 1
Dresden, , Germany
Universitätsklinikum Essen
Essen, , Germany
Klinik Esslingen
Esslingen am Neckar, , Germany
Klinikum Frankfurt/Oder
Frankfurt (Oder), , Germany
Uniklinikum Freiburg
Freiburg im Breisgau, , Germany
Universitaetsklinikum Heidelberg
Heidelberg, , Germany
Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte
Herne, , Germany
Praxisklinik für Hämatologie und Onkologie Koblenz
Koblenz, , Germany
Kliniken Maria Hilf GmbH Innere Medizin I
Mönchengladbach, , Germany
Klinikum Schwäbisch Gmünd
Mutlangen, , Germany
München Klinik Schwabing
München, , Germany
Klinikum rechts der Isar der Technischen Universität München
München, , Germany
Klinikum der Universität München, Campus Großhadern
München, , Germany
Brüderkrankenhaus St. Josef Paderborn
Paderborn, , Germany
Krankenhaus Barmherzige Bruder Regensburg
Regensburg, , Germany
Marienhospital
Stuttgart, , Germany
Robert-Bosch-Krankenhaus
Stuttgart, , Germany
Universitatsklinikum Tubingen
Tübingen, , Germany
Universtitätsklinikum Ulm
Ulm, , Germany
Arcispedale S. Anna
Ferrara, Emilia-Romagna, Italy
Uni Cattolica
Rome, Lazio, Italy
AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette
Torino, Lazio, Italy
Ospedale San Raffaele
Milan, Lombardy, Italy
Az. Osp. S. Maria
Terni, Umbria, Italy
Ospedale dell' Angelo
Venezia Mestre, Veneto, Italy
Hospital General de Culiacan
Culiacán, Sinaloa, Mexico
Canterbury Health Laboratories
Christchurch, , New Zealand
Dunedin Hospital
Dunedin, , New Zealand
Midcentral District Health Board
Palmerston North, , New Zealand
Wellington Hospital
Wellington, , New Zealand
Samodzielny Public Zaklad
Chorzów, , Poland
Wojewódzki Szpital Specjalistyczny im. Miko?aja Kopernika
Lodz, , Poland
Wojewodzki Szpital Specjalistyczny im. J. Korczaka
Słupsk, , Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroc?awiu
Wroclaw, , Poland
Fundeni Clinical Inst.
Bucharest, , Romania
Institutul Regional de Oncologie Iasi
Iași, , Romania
Spitalul Clinic Judetean de Urgenta Targu-Mures
Târgu Mureş, , Romania
SBEI of HPE ?Bashkir State Medical University? of MoH RF
Ufa, Bashkortostan Republic, Russia
Regional Clinical Hospital N.A. Semashko
Nizhny Novgorod, Niznij Novgorod, Russia
Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
Kazan', Tatarstan Republic, Russia
Penza Regional Oncology Dispensary
Penza, , Russia
Clinical MSCh No1
Perm, , Russia
Complejo Hospitalario de Navarra
Pamplona, Navarre, Spain
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Tenerife, Spain
Hospital del Mar
Barcelona, , Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital Clínic i Provincial
Barcelona, , Spain
Hospital Universitario de la Princesa
Madrid, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Hospital Univ. 12 de Octubre
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Clinico Universitario de Salamanca
Salamanca, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Complejo Hospitalario de Toledo- H. Virgen de la Salud
Toledo, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia
Valencia, , Spain
Inselspital Bern
Bern, , Switzerland
Luzerner Kantonsspital, Hämatologie
Lucerne, , Switzerland
Universitätsspital Zürich Medizin Hämatologie
Zurich, , Switzerland
Birmingham Heartlands Hospital
Birmingham, , United Kingdom
Boston Pilgrim Hospital
Boston,Lincolnshire, , United Kingdom
Western General Hospital
Edinburgh, , United Kingdom
Lincoln County Hospital
Lincoln, , United Kingdom
University Hospital Southampton NHS Foundation Trust
Southhampton, , United Kingdom
Countries
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References
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Munir T, Martinez-Calle N, Xu S, Yang K, Ge X, Ali AK, Mohseninejad L, Dobi B, Rakonczai P, Ma H, Williams R, Aldairy W, Lamanna N. Indirect Comparisons of the Efficacy and Safety of Zanubrutinib versus Venetoclax plus Obinutuzumab in Treatment-Naive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Oncol Ther. 2025 Sep 13. doi: 10.1007/s40487-025-00380-0. Online ahead of print.
Al-Sawaf O, Robrecht S, Zhang C, Olivieri S, Chang YM, Fink AM, Tausch E, Schneider C, Ritgen M, Kreuzer KA, Sivchev L, Niemann CU, Schwarer A, Loscertales J, Weinkove R, Strumberg D, Kilfoyle A, Manzoor BS, Jawaid D, Emechebe N, Devine J, Boyer M, Runkel ED, Eichhorst B, Stilgenbauer S, Jiang Y, Hallek M, Fischer K. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study. Blood. 2024 Oct 31;144(18):1924-1935. doi: 10.1182/blood.2024024631.
Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.
Al-Sawaf O, Zhang C, Jin HY, Robrecht S, Choi Y, Balasubramanian S, Kotak A, Chang YM, Fink AM, Tausch E, Schneider C, Ritgen M, Kreuzer KA, Chyla B, Paulson JN, Pallasch CP, Frenzel LP, Peifer M, Eichhorst B, Stilgenbauer S, Jiang Y, Hallek M, Fischer K. Transcriptomic profiles and 5-year results from the randomized CLL14 study of venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab in chronic lymphocytic leukemia. Nat Commun. 2023 Apr 18;14(1):2147. doi: 10.1038/s41467-023-37648-w.
Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.
Samineni D, Gibiansky L, Wang B, Vadhavkar S, Rajwanshi R, Tandon M, Sinha A, Al-Sawaf O, Fischer K, Hallek M, Salem AH, Li C, Miles D. Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Adv Ther. 2022 Aug;39(8):3635-3653. doi: 10.1007/s12325-022-02170-w. Epub 2022 Jun 16.
Al-Sawaf O, Zhang C, Lu T, Liao MZ, Panchal A, Robrecht S, Ching T, Tandon M, Fink AM, Tausch E, Schneider C, Ritgen M, Bottcher S, Kreuzer KA, Chyla B, Miles D, Wendtner CM, Eichhorst B, Stilgenbauer S, Jiang Y, Hallek M, Fischer K. Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study. J Clin Oncol. 2021 Dec 20;39(36):4049-4060. doi: 10.1200/JCO.21.01181. Epub 2021 Oct 28.
Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5.
Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019 Jun 6;380(23):2225-2236. doi: 10.1056/NEJMoa1815281. Epub 2019 Jun 4.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2014-001810-24
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CLL14
Identifier Type: -
Identifier Source: secondary_id
BO25323
Identifier Type: -
Identifier Source: org_study_id
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