A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT ID: NCT03462719
Last Updated: 2025-11-13
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE3
211 participants
INTERVENTIONAL
2018-04-17
2029-04-05
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)
Participants will initially receive ibrutinib (420 mg \[milligrams\]/day) for 3 cycles. Venetoclax dose ramp up (from 20 to 400 mg over 5 weeks) will begin at Cycle 4 and the combination of ibrutinib and venetoclax will be given for 12 cycles (each cycle is equivalent to 28 days). Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.
Ibrutinib
Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles.
Venetoclax
Participants will receive venetoclax in combination with ibrutinib for a total of 12 cycles, beginning at Cycle 4. For the first 5 weeks of venetoclax treatment, the treatment dose will be ramped up from 20 to 400 mg.
Ibrutinib (as Subsequent Therapy)
Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)
Participants will receive chlorambucil and obinutuzumab (G-Clb) for 6 cycles. Participants will receive obinutuzumab, 1000 mg intravenously (IV) on Days 1, 8 and 15 of Cycle 1, and on Day 1 of Cycles 2 to 6 and chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight, on Days 1 and 15 of Cycles 1 to 6. Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.
Chlorambucil
Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6.
Obinutuzumab
Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6.
Ibrutinib (as Subsequent Therapy)
Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ibrutinib
Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles.
Venetoclax
Participants will receive venetoclax in combination with ibrutinib for a total of 12 cycles, beginning at Cycle 4. For the first 5 weeks of venetoclax treatment, the treatment dose will be ramped up from 20 to 400 mg.
Chlorambucil
Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6.
Obinutuzumab
Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6.
Ibrutinib (as Subsequent Therapy)
Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Cumulative Illness Rating Scale (CIRS) score \> 6
2. Creatinine clearance (CrCl) estimated less than (\<) 70 milliliter per minute (mL/min) using Cockcroft-Gault equation
* Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
* Measurable nodal disease (by computed tomography \[CT\]), defined as at least one lymph node \> 1.5 centimeter (cm) in longest diameter
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade less than or equal to (\<=) 2
* Active CLL/SLL requiring treatment per the iwCLL criteria
Exclusion Criteria
* Presence of deletion of the short arm of chromosome 17 (del17p) or known TP53 mutation detected at a threshold of \>10 percent (%) variable allele frequency (VAF)
* Major surgery within 4 weeks of first dose of study treatment
* Known bleeding disorders (example, von Willebrand's disease or hemophilia)
* Central nervous system (CNS) involvement or suspected Richter's syndrome
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Pharmacyclics LLC.
INDUSTRY
Janssen Research & Development, LLC
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Janssen Research & Development, LLC Clinical Trial
Role: STUDY_DIRECTOR
Janssen Research & Development, LLC
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Norton Cancer Institute
Louisville, Kentucky, United States
John Theurer Cancer Center
Hackensack, New Jersey, United States
Novant Health
Charlotte, North Carolina, United States
Institut - Jules Bordet
Anderlecht, , Belgium
ZNA Stuivenberg
Antwerp, , Belgium
Universitair Ziekenhuis Gent
Ghent, , Belgium
Virga Jessa Ziekenhuis
Hasselt, , Belgium
UZ Leuven Gasthuisberg
Leuven, , Belgium
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
Juravinski Cancer Centre
Hamilton, Ontario, Canada
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada
CIUSSS de l Est de l Ile de Montreal Installation Hopital Maisonneuve Rosemont
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika
Brno, , Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, , Czechia
Fakultni Nemocnice Ostrava
Ostrava, , Czechia
Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
Pilsen, , Czechia
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
Prague, , Czechia
Aalborg University Hospital
Aalborg, , Denmark
Aarhus Universitetshospital
Aarhus, , Denmark
Rigshospitalet
Copenhagen, , Denmark
Odense Universitetshospital
Odense C, , Denmark
Roskilde Sygehus
Roskilde, , Denmark
CHU de Clermont Ferrand
Clermont-Ferrand, , France
Hopital Claude Huriez
Lille, , France
CHU Montpellier
Montpellier, , France
Hopital Haut Leveque Service Maladie Du Sang
Pessac, , France
Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré
Reims, , France
Institut Universitaire du Cancer Toulouse Oncopole
Toulouse, , France
CHU Bretonneau
Tours, , France
CHU-Nancy
Vandœuvre-lès-Nancy, , France
Institut Gustave Roussy
Villejuif, , France
Bnai Zion Medical Center
Haifa, , Israel
Carmel Medical Center
Haifa, , Israel
Hadassah Medical Center
Jerusalem, , Israel
Western Galilee Medical Center
Nahariya, , Israel
Sheba Medical Center
Ramat Gan, , Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, , Israel
Flevoziekenhuis
Almere Stad, , Netherlands
OLVG
Amsterdam, , Netherlands
Academic Medical Center
Amsterdam, , Netherlands
Reinier de Graaf Gasthuis
Delft, , Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, , Netherlands
Catharinaziekenhuis
Eindhoven, , Netherlands
Spaarne Gasthuis
Hoofddorp, , Netherlands
Zuyderland Medical Center
Sittard-Geleen, , Netherlands
Antonius hospital
Sneek, , Netherlands
MC Haaglanden
The Hague, , Netherlands
Elisabeth zkh
Tilburg, , Netherlands
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
Chorzów, , Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
Lodz, , Poland
Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie
Lublin, , Poland
Wojewodzki Szpital Specjalistyczny im Janusza Korczaka
Słupsk, , Poland
Instytut Hematologii i Transfuzjologii
Warsaw, , Poland
Moscow Multidisciplinary Scientific and Clinical Center named after S P Botkin
Moscow, , Russia
S.P. Botkin Moscow City Clinical Hospital
Moscow, , Russia
Nizhniy Novgorod Region Clinical Hospital
Nizhny Novgorod, , Russia
Ryazan Regional Clinical Hospital
Ryazan, , Russia
St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
Saint Petersburg, , Russia
FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF
Saint Petersburg, , Russia
Hosp Univ Vall D Hebron
Barcelona, , Spain
Hosp Clinic de Barcelona
Barcelona, , Spain
Hosp. de La Santa Creu I Sant Pau
Barcelona, , Spain
Hosp. Univ. de La Princesa
Madrid, , Spain
Hosp. Gral. Univ. Gregorio Maranon
Madrid, , Spain
Hosp. Univ. Infanta Leonor
Madrid, , Spain
Hospital Ramon y Cajal
Madrid, , Spain
Hosp Univ Fund Jimenez Diaz
Madrid, , Spain
Clinica Univ. de Navarra
Pamplona, , Spain
Hospital Clinico Universitario Salamanca
Salamanca, , Spain
Hosp. Virgen Del Rocio
Seville, , Spain
Sunderby Sjukhus Medicinkliniken
Luelå, , Sweden
Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm
Stockholm, , Sweden
Gazi Universitesi Tip Fakultesi
Ankara, , Turkey (Türkiye)
Ankara Universitesi Tip Fakültesi Ibn-i Sina Hastanesi
Ankara, , Turkey (Türkiye)
Ondokuz Mayis University
Atakum, , Turkey (Türkiye)
V K V Amerikan Hastanesi
Istanbul, , Turkey (Türkiye)
Dokuz Eylul Universitesi Tip Fakultesi
Izmir, , Turkey (Türkiye)
Birmingham Heartlands Hospital
Birmingham, , United Kingdom
Addenbrookes Hospital
Cambridge, , United Kingdom
Queen Mary University of London
Charterhouse Square, , United Kingdom
New Victoria Hospital
Glasgow, , United Kingdom
St James's Hospital
Leeds, , United Kingdom
Derriford Hospital
Plymouth, , United Kingdom
Barking Havering and Redbridge University Hospitals NHS Trust
Romford, , United Kingdom
Royal Hallamshire Hospital
Sheffield, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Kater AP, Owen C, Moreno C, Follows G, Munir T, Levin MD, Benjamini O, Janssens A, Osterborg A, Robak T, Simkovic M, Stevens D, Voloshin S, Vorobyev V, Ysebaert L, Qin R, Steele AJ, Schuier N, Baeten K, Caces DB, Niemann CU. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. NEJM Evid. 2022 Jul;1(7):EVIDoa2200006. doi: 10.1056/EVIDoa2200006. Epub 2022 May 13.
Niemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, Janssens A, Levin MD, Robak T, Simkovic M, Voloshin S, Vorobyev V, Yagci M, Ysebaert L, Qi K, Qi Q, Sinet P, Parisi L, Srinivasan S, Schuier N, Baeten K, Howes A, Caces DB, Kater AP. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1423-1433. doi: 10.1016/S1470-2045(23)00452-7. Epub 2023 Nov 6.
Moreno C, Solman IG, Tam CS, Grigg A, Scarfo L, Kipps TJ, Srinivasan S, Mali RS, Zhou C, Dean JP, Szafer-Glusman E, Choi M. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study. Blood Adv. 2023 Sep 26;7(18):5294-5303. doi: 10.1182/bloodadvances.2023010236.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2017-004699-77
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
54179060CLL3011
Identifier Type: OTHER
Identifier Source: secondary_id
CR108428
Identifier Type: -
Identifier Source: org_study_id