Ibrutinib Monotherapy Versus Fixed-duration Venetoclax Plus Obinutuzumab Versus Fixed-duration Ibrutinib Plus Venetoclax in Patients With Previously Untreated Chronic Lymphocytic Leukaemia (CLL)
CLL17
A Phase 3 Multicentre, Randomized, Prospective, Open-label Trial of Ibrutinib Monotherapy Versus Fixed-duration Venetoclax Plus Obinutuzumab Versus Fixed-duration Ibrutinib Plus Venetoclax in Patients With Previously Untreated Chronic Lymphocytic Leukaemia (CLL)
3 other identifiers
interventional
897
13 countries
181
Brief Summary
The aim of this study is to compare the efficacy of continuous ibrutinib monotherapy with fixed-duration venetoclax plus obinutuzumab and fixed-duration ibrutinib plus venetoclax by measuring progression-free survival (PFS) in patients with previously untreated CLL.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2021
Longer than P75 for phase_3
181 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 23, 2020
CompletedFirst Posted
Study publicly available on registry
October 29, 2020
CompletedStudy Start
First participant enrolled
March 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
April 30, 2026
April 1, 2026
6.5 years
October 23, 2020
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Investigator-assessed progression-free survival (PFS)
Time from randomization to the first occurrence of progression or relapse (determined using standard iwCLL guidelines), or death from any cause, whichever occurs first
Up to 80 month
Secondary Outcomes (9)
Rates of undetectable minimal residual disease (uMRD) in peripheral blood (PB) and bone marrow (BM)
At final restaging (RE): 18 months after start of treatment and additional BM assessment approx. 12 months after RE
MRD levels in PB at different time points
Up to 80 month
Overall response rate (ORR)
At final restaging (RE): 18 months after start of treatment
CR/CRi rate
At final restaging (RE): 18 months after start of treatment
Event-free survival
Up to 80 month
- +4 more secondary outcomes
Study Arms (3)
I (Ibrutinib)
EXPERIMENTALIbrutinib p.o. will be administered until occurrence of unacceptable toxicity, progression of CLL or end of trial, whichever occurs first.
VG (Obinutuzumab + Venetoclax)
EXPERIMENTAL12 cycles (q 28d): Obinutuzumab i.v. + Venetoclax p.o. will be administered for 6 cycles, followed by 6 additional cycles of Venetoclax alone
VI (Venetoclax + Ibrutinib)
EXPERIMENTAL15 cycles (q 28d): Ibrutinib p.o. + Venetoclax p.o. will be administered for a total of 12 cycles with a prior Ibrutinib monotherapy lead-in of 3 cycles
Interventions
Cycles 1 - X: 420 mg daily, d1-28 p.o.
Arm VG Cycle 1: 20 mg (2 tabl. at 10 mg), d22-28 p.o. Cycle 2: 50 mg (1 tabl. at 50 mg), d1-7; 100 mg (1 tabl. at 100 mg), d8-14; 200 mg (2 tabl. at 100 mg), d15-21; 400 mg (4 tabl. at 100 mg), d22-28 p.o. Cycles 3-12: 400 mg (4 tabl. at 100 mg), d1-28 p.o. Arm VI Cycle 4: 20 mg (2 tabl. at 10 mg), d1-7; 50 mg (1 tabl. at 50 mg), d8-14; 100 mg (1 tabl. at 100 mg), d15-21; 200 mg (2 tabl. at 100 mg), d22-28 p.o. Cycles 5-15: 400 mg (4 tabl. at 100 mg), d1-28 p.o.
Cycle 1: (100 mg, d1 + 900 mg, d2) or 1000 mg, d1; 1000 mg, d8 + d15 i.v. Cycle 2 - 6: 1000 mg, d1 i.v.
Eligibility Criteria
You may qualify if:
- Documented CLL requiring treatment according to iwCLL criteria.
- Age at least 18 years.
- Life expectancy ≥ 6 months.
- Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
- Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of screening initiation as follows, unless cytopenia is due to CLL:
- Absolute neutrophil count ≥ 1.0 × 109/L
- Platelet counts ≥ 30 × 109/L; in cases of thrombocytopenia clearly due to CLL (per the discretion of the investigator), platelet count should be ≥ 10 × 109/L
- Total haemoglobin ≥ 8 g/dL (without transfusion support, unless anaemia is due to CLL)
- GFR \>30ml/min directly measured with 24hr urine collection, calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight)/ (72 x creatinine), for women x 0, 85) or an equally accurate method.
- a. For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 30 ml/min may be eligible if a repeat estimate after adequate hydration is \> 30 ml/min.
- Adequate liver function as indicated by a total bilirubin ≤ 2 x, AST/ ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome.
- Negative serological testing for hepatitis B (HbsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month/every three months if persistently negative until 12 months after last treatment cycle), and for hepatitis C (anti-HCV-ab negative; in case of positive HCV anti-body test, negative HCV-PCR is required).
- Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.
You may not qualify if:
- Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents up to 20 mg prednisolone are permitted).
- Transformation of CLL (Richter transformation). When Richter transformation is suspected, PET-CT and/or biopsy should be performed to rule out transformation.
- Patients with a history of PML.
- An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the study treatment or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could compromise the patients' safety or interfere with the absorption or metabolism of the study drugs (e.g. inability to swallow tablets or impaired resorption in the gastrointestinal tract).
- Malignancies other than CLL currently requiring systemic therapies, not being treated with curative intent before (unless the malignant disease is in a stable remission due to the discretion of the treating physician or showing signs of progression after curative treatment.
- Uncontrolled or active infection.
- Patients with known infection with human immunodeficiency virus (HIV).
- Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/ inducers (incl. up to 7 days prior to study treatment start).
- Anticoagulant therapy with warfarin, phenprocoumon or other vit-amin K antagonists (alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly informed about the potential risk of bleeding under treatment with ibrutinib).
- History of stroke or intracranial hemorrhage within 6 months prior to registration for study screening.
- Known bleeding disorders
- Child B / C liver cirrhosis
- Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
- Vaccination with live vaccines 28 days prior to registration for study screening.
- Major surgery less than 30 days before start of study treatment.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- German CLL Study Grouplead
- Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)collaborator
- Nordic CLL Study Group (NCLLSG)collaborator
- Swiss Group for Clinical Cancer Research (SAKK)collaborator
- Cancer Trials Irelandcollaborator
- Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA)collaborator
- Grupo Español de Leucemia Linfocítica Crónica (GELLC)collaborator
- The Israeli CLL Study Group (ICLLSG)collaborator
- Janssen Pharmaceutica N.V., Belgiumcollaborator
- AbbViecollaborator
- Hoffmann-La Rochecollaborator
Study Sites (181)
LKH-Universtitätsklinikum Graz
Graz, 8036, Austria
Landeskrankenhaus - Universitätskliniken Innsbruck
Innsbruck, 6020, Austria
Medizinische Universität Wien
Vienna, 1090, Austria
Hanusch Krankenhaus
Vienna, 1140, Austria
Wiener Gesundheitsverbund Klinik Ottakring
Vienna, 1160, Austria
Algemeen Ziekenhuis St. Jan
Bruges, 8000, Belgium
Universitair Ziekenhuis Leuven
Leuven, 3000, Belgium
Algemeen Ziekenhuis Delta
Roeselare, 8800, Belgium
Aalborg Universitetshospital
Aalborg, 9000, Denmark
Aarhus Universitetshospital
Aarhus, 8200, Denmark
Rigshospitalet
Copenhagen, 2100, Denmark
Sydvestjysk Sygehus Esbjerg
Esbjerg, 6700, Denmark
Regionshospitalet Holstebro
Holstebro, 7500, Denmark
Odense Universitetshospital
Odense, 5000, Denmark
Zealand University Hospital
Roskilde, 4000, Denmark
Lillebaelt Vejle Sygehus
Vejle, 7100, Denmark
Helsinki University Hospital
Helsinki, 29, Finland
Tampere University Hospital
Tampere, 33520, Finland
Turku University Hospital
Turku, 20521, Finland
Universitätsklinikum Augsburg
Augsburg, 86156, Germany
Onkologische Schwerpunktpraxis Kurfürstendamm
Berlin, 10707, Germany
Charite Universitaetsmedizin - Campus Benjamin Franklin
Berlin, 12203, Germany
Helios Klinikum Berlin Buch
Berlin, 13125, Germany
Charite Universitätsmedizin - Campus Virchow Klinikum
Berlin, 13353, Germany
Ev. Diakoniekrankenhaus
Bremen, 28239, Germany
Universitätsklinik Köln
Cologne, 50924, Germany
Gemeinschaftspraxis für Hämatologie & Onkologie
Dortmund, 44263, Germany
Gemeinschaftspraxis Hämatologie Onkologie
Dresden, 1307, Germany
Universitätsklinik Carl Gustav Carus
Dresden, 1307, Germany
Sana Krankenhaus Benrath
Düsseldorf, 40593, Germany
St. Georg Klinikum Eisenach
Eisenach, 99817, Germany
ISP Erlangen Onkologische Schwerpunktpraxis
Erlangen, 91052, Germany
Universitätsklinikum Erlangen
Erlangen, 91054, Germany
Universitaetsklinikum Essen
Essen, 45147, Germany
Onkologische Schwerpunktpraxis
Esslingen am Neckar, 73728, Germany
Centrum für Hämatologie und Onkologie Bethanien
Frankfurt, 60389, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Uniklinikum Gießen und Marburg
Giessen, 35392, Germany
MVZ Onkologische Kooperation Harz
Goslar, 38642, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
OncoResearch Lerchenfeld
Hamburg, 22081, Germany
Evangelische Krankenhaus Hamm
Hamm, 59063, Germany
Onkologisches Ambulanzzentrum - MediProjekt
Hanover, 30171, Germany
Onkologische Schwerpunktpraxis Heidelberg
Heidelberg, 69115, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Marien Hospital Herne
Herne, 44625, Germany
Universitätskliniken des Saarlandes
Homburg, 66424, Germany
Universitätsklinikum Jena
Jena, 7747, Germany
Westpfalz-Klinikum GmbH
Kaiserslautern, 67655, Germany
Universitaetsklinikum Schleswig-Holstein Campus Kiel
Kiel, 24105, Germany
Praxis für Haematologie und Onkologie
Koblenz, 56068, Germany
MVZ Hämatologie Onkologie Koblenz
Koblenz, 56727, Germany
H.O.T Onkologie Praxis Landshut
Landshut, 84036, Germany
Universitätsklinikum Leipzig
Leipzig, 4103, Germany
Onkopraxis Probstheida
Leipzig, 4289, Germany
Klinikum Lippe Lemgo
Lemgo, 32657, Germany
St Vincenz Krankenhaus
Limburg, 65549, Germany
Lübecker Onkologische Schwerpunktpraxis
Lübeck, 23562, Germany
Gemeinschaftspraxis Haematologie und Onkologie
Magdeburg, 39104, Germany
Universitätsklinikum Magdeburg
Magdeburg, 39120, Germany
Mannheimer Onkologie Praxis
Mannheim, 68161, Germany
Praxis für Innere Medizin - Hämatologie und Onkologie
Marburg, 35037, Germany
Kliniken Maria Hilf
Mönchengladbach, 41063, Germany
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557, Germany
München Klinik Schwabing
München, 80804, Germany
Klinikum der Universitaet München - Grosshadern Campus
München, 81377, Germany
Klinikum rechts der Isar - Technische Universitaet Muenchen
München, 81675, Germany
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, 48153, Germany
Klinikum Oldenburg
Oldenburg, 26133, Germany
Brüderkrankenhaus St. Josef Paderborn
Paderborn, 33098, Germany
Gemeinschaftspraxis für Hämatologie und Onkologie
Ravensburg, 88212, Germany
Barmherzigen Brüder Krankenhaus
Regensburg, 93049, Germany
Schwerpunktpraxis für Hämatologie & Onkologie - OncoPro GbR
Regensburg, 93053, Germany
Universitätsklinik Rostock
Rostock, 18057, Germany
OnkoSaar Praxis für Hämatologie und Onkologie
Saarbrücken, 66113, Germany
Zentrum für abulante Hämatologie und Onkologie
Siegburg, 53721, Germany
Marienhospital Stuttgart
Stuttgart, 70199, Germany
Robert-Bosch-Krankenhaus
Stuttgart, 70376, Germany
Universitätsklinik Tübingen
Tübingen, 72076, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
MVZ Weiden GmbH
Weiden, 92637, Germany
Hämatologisch Onkologische Schwerpunktpraxis
Würzburg, 97080, Germany
Cork University Hospital
Cork, T12DC4A, Ireland
St Vincents University Hospital
Dublin, Dublin 4, Ireland
Mater Misericordiae University Hospital
Dublin, Dublin 7, Ireland
St. James's Hospital
Dublin, Dublin 8, Ireland
Beaumont Hospital
Dublin, Dublin 9, Ireland
University Hospital Galway
Galway, H91 YR71, Ireland
University Hospital Limerick
Limerick, V94 F858, Ireland
University Hospital Waterford
Waterford, X91 ER8E, Ireland
Soroka University Medical Center
Beersheba, 84101, Israel
Shamir Medical Center Assaf Harofeh
Be’er Ya‘aqov, 70300, Israel
Bnai-Zion Medical Center
Haifa, 31048, Israel
Hadassah Medical Center Ein Kerem University Hospital
Jerusalem, 91120, Israel
Meir Medical Center
Kfar Saba, 4428164, Israel
Galilee Medical Center
Nahariya, 22100, Israel
Rabin Medical Center Beilinson Hospital
Petah Tikva, 4941492, Israel
Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Kaplan Medical Center
Rehovot, 7610001, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
Catania, 9513, Italy
Azienda Ospedaliero Universitaria di Ferrara
Ferrara, 44124, Italy
Ospedale dell'Angelo
Mestre, 30174, Italy
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
Milan, 20122, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
IRCCS Ospedale San Raffaele
Milan, 202132, Italy
Ospedale S. Maria della Misericordia
Perugia, 6123, Italy
Umberto I - Policlinico di Roma - Sapienza Università
Roma, 161, Italy
Gmelli University Hospital
Roma, 168, Italy
Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
Torino, 10126, Italy
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223GZ, Netherlands
Nordwest Ziekenhuisgroep, Locatie Alkmaar
Alkmaar, 1815JD, Netherlands
OLVG Amsterdam
Amsterdam, 1091AC, Netherlands
Amsterdam Universitair Medische Centra
Amsterdam, 1105AZ, Netherlands
Rijnstate, Locatie Arnhem
Arnhem, 6815AD, Netherlands
Amphia Ziekenhuis
Breda, 4818CK, Netherlands
Reinier de Graaf Ziekenhuis
Delft, 2625AD, Netherlands
Slingeland ziekenhuis
Doetinchem, 7009BL, Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, 3318AT, Netherlands
Ziekenhuis Gelderse Vallei
Ede, 6716RP, Netherlands
Martini Ziekenhuis
Groningen, 9728NT, Netherlands
Ziekenhuis St Jansdal
Harderwijk, 3844DG, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, 8934AD, Netherlands
Alrijne Ziekenhuis
Leiderdorp, 2353GA, Netherlands
St. Antonius Ziekenhuis
Nieuwegein, 3435CM, Netherlands
Canisius-Wilhelmina Ziekenhuis
Nijmegen, 6532SZ, Netherlands
Maasstad Ziekenhuis
Rotterdam, 3079DZ, Netherlands
Franciscus Vlietland
Schiedam, 3118JH, Netherlands
Ziekenhuis Rivierenland Tiel
Tiel, 4002WP, Netherlands
Diakonessenhuis
Utrecht, 3582 KE, Netherlands
VieCuri Medish Centrum
Venlo, 5912BL, Netherlands
Isala Zwolle
Zwolle, 8025AB, Netherlands
Haukeland University Hospital
Bergen, 5021, Norway
Akershus University Hospital
Lørenskog, 1478, Norway
Oslo University Hospital
Oslo, 372, Norway
St. Olavs Hospital Trondheim University Hospital
Trondheim, 7030, Norway
Hospital Germans Trias i Pujol
Badalona, 8916, Spain
Vall d'Hebron University Hospital
Barcelona, 8035, Spain
Hospital Clinic de Barcelona
Barcelona, 8036, Spain
Hospital Duran i Reynals
Barcelona, 8908, Spain
Hospital Universitario La Princesa
Madrid, 28006, Spain
Hospital Universitario Infanta Leonor
Madrid, 28031, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Costa del Sol
Málaga, 29603, Spain
Hospital Universitario Central de Asturias
Oviedo, 33011, Spain
Hospital Clinico Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Marques de Valdecilla
Santander, 39008, Spain
Hospital Universitario Virgen de Valme
Seville, 41014, Spain
Hospital Clinico Universitario Valencia
Valencia, 46010, Spain
Residencia Sanitaria La Fe - Valencia
Valencia, 46026, Spain
Hospital Clinico Universitario Lozano Blesa
Zaragoza, 50009, Spain
Soedra Aelvsborgs Sjukhus
Borås, 50182, Sweden
Falu Lasarett
Falun, 79182, Sweden
Sahlgrenska University Hospital
Gothenburg, 41346, Sweden
Hallands Sjukhus Halmstad
Halmstad, 30185, Sweden
Universitetssjukhuset Linköping
Linköping, 58185, Sweden
Sunderby Hospital
Luleå, 97180, Sweden
Skåne University Hospital
Lund, 22185, Sweden
Örebro University Hospital
Örebro, 70185, Sweden
Karolinska University Hospital Solna
Stockholm, 17176, Sweden
Umeå University Hospital
Umeå, 90185, Sweden
Uppsala University Hospital
Uppsala, 75185, Sweden
Hallands Sjukhus
Varberg, 43281, Sweden
Kantonsspital Aarau
Aarau, 5001, Switzerland
Kantonsspital Baden
Baden, 5404, Switzerland
Universitätsspital Basel
Basel, 4031, Switzerland
Ospedale Regionale Bellinzona e Valli
Bellinzona, 6500, Switzerland
Inselspital Bern
Bern, 3010, Switzerland
Spitalzentrum Oberwallis
Brig, 3900, Switzerland
Kantonsspital Graubünden
Chur, 7000, Switzerland
HFR Fribourg Hôpital cantonal
Fribourg, 1708, Switzerland
Hôpitaux Universitaires Genève
Geneva, 1211, Switzerland
Kantonsspital Baselland
Liestal, 4410, Switzerland
Luzerner Kantonsspital
Lucerne, 6000, Switzerland
Spital Thurgau AG - Kantonsspital Münsterlingen
Münsterlingen, 8596, Switzerland
Kantonsspital Olten
Olten, 4600, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, 9007, Switzerland
Spital Thun
Thun, 3600, Switzerland
Kantonsspital Winterthur
Winterthur, 8401, Switzerland
Stadtspital Triemli
Zurich, 8063, Switzerland
Universitätsspital Zuerich
Zurich, 8091, Switzerland
Related Publications (1)
Al-Sawaf O, Stumpf J, Zhang C, Simon F, Bosch F, Feyzi E, Ghia P, Gregor M, Kater AP, Lindstrom V, Mattsson M, Niemann CU, Staber PB, Tadmor T, Thornton P, Wendtner CM, Janssens A, Noesslinger T, Bohn JP, da Cunha-Bang C, Poulsen CB, Ranti J, Illmer T, Schoettker B, Bottcher S, Gaska T, Vandenberghe E, Clifford R, Benjamini O, Frustaci AM, Scarfo L, Sportoletti P, Schreurs J, Levin MD, van der Straaten H, van der Klift M, Tran H, de la Serna J, Loscertales J, Lindblad O, Bergendahl Sandstedt A, Goede J, Baumann M, Fink AM, Fischer K, Ritgen M, Kreuzer KA, Schneider C, Tausch E, Stilgenbauer S, Robrecht S, Eichhorst B, Hallek M; CLL17 Trial Investigators. Fixed-Duration versus Continuous Treatment for Chronic Lymphocytic Leukemia. N Engl J Med. 2026 Mar 12;394(11):1084-1096. doi: 10.1056/NEJMoa2515458. Epub 2025 Dec 6.
PMID: 41358601DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Othman Al-Sawaf, Dr. med.
German CLL Study Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 23, 2020
First Posted
October 29, 2020
Study Start
March 1, 2021
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
September 1, 2027
Last Updated
April 30, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share