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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphoid Leukemia
• Intervention / Treatment: Biological: Ibrutinib; Biological: Venetoclax; Biological: Obinutuzumab

• Study Type: Interventional
• Enrollment (Estimated): 897
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH-Universtitätsklinikum Graz
  • Innsbruck, Austria, 6020
    • Landeskrankenhaus - Universitätskliniken Innsbruck
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien
  • Vienna, Austria, 1140
    • Hanusch Krankenhaus
  • Vienna, Austria, 1160
    • Wiener Gesundheitsverbund Klinik Ottakring
• Belgium
  • Bruges, Belgium, 8000
    • Algemeen Ziekenhuis St. Jan
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
  • Roeselare, Belgium, 8800
    • Algemeen Ziekenhuis Delta
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Esbjerg, Denmark, 6700
    • Sydvestjysk Sygehus Esbjerg
  • Holstebro, Denmark, 7500
    • Regionshospitalet Holstebro
  • Odense, Denmark, 5000
    • Odense Universitetshospital
  • Roskilde, Denmark, 4000
    • Zealand University Hospital
  • Vejle, Denmark, 7100
    • Lillebaelt Vejle Sygehus
• Finland
  • Helsinki, Finland, 29
    • Helsinki University Hospital
  • Tampere, Finland, 33520
    • Tampere University Hospital
  • Turku, Finland, 20521
    • Turku University Hospital
• Germany
  • Augsburg, Germany, 86156
    • Universitätsklinikum Augsburg
  • Berlin, Germany, 10707
    • Onkologische Schwerpunktpraxis Kurfürstendamm
  • Berlin, Germany, 13125
    • HELIOS Klinikum Berlin Buch
  • Berlin, Germany, 12203
    • Charite Universitaetsmedizin - Campus Benjamin Franklin
  • Berlin, Germany, 13353
    • Charite Universitätsmedizin - Campus Virchow Klinikum
  • Bremen, Germany, 28239
    • Ev. Diakoniekrankenhaus
  • Cologne, Germany, 50924
    • Universitätsklinik Köln
  • Dortmund, Germany, 44263
    • Gemeinschaftspraxis für Hämatologie & Onkologie
  • Dresden, Germany, 1307
    • Gemeinschaftspraxis Hämatologie Onkologie
  • Dresden, Germany, 1307
    • Universitätsklinik Carl Gustav Carus
  • Düsseldorf, Germany, 40593
    • Sana Krankenhaus Benrath
  • Eisenach, Germany, 99817
    • St. Georg Klinikum Eisenach
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Erlangen, Germany, 91052
    • ISP Erlangen Onkologische Schwerpunktpraxis
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Esslingen am Neckar, Germany, 73728
    • Onkologische Schwerpunktpraxis
  • Frankfurt, Germany, 60389
    • Centrum fur Hamatologie und Onkologie Bethanien
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg
  • Giessen, Germany, 35392
    • Uniklinikum Gießen und Marburg
  • Goslar, Germany, 38642
    • MVZ Onkologische Kooperation Harz
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 22081
    • OncoResearch Lerchenfeld
  • Hamm, Germany, 59063
    • Evangelische Krankenhaus Hamm
  • Hanover, Germany, 30171
    • Onkologisches Ambulanzzentrum - MediProjekt
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Heidelberg, Germany, 69115
    • Onkologische Schwerpunktpraxis Heidelberg
  • Herne, Germany, 44625
    • Marien Hospital Herne
  • Homburg, Germany, 66424
    • Universitätskliniken des Saarlandes
  • Jena, Germany, 7747
    • Universitätsklinikum Jena
  • Kaiserslautern, Germany, 67655
    • Westpfalz-Klinikum GmbH
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein Campus Kiel
  • Koblenz, Germany, 56068
    • Praxis für Haematologie und Onkologie
  • Koblenz, Germany, 56727
    • MVZ Hämatologie Onkologie Koblenz
  • Landshut, Germany, 84036
    • H.O.T Onkologie Praxis Landshut
  • Leipzig, Germany, 4103
    • Universitätsklinikum Leipzig
  • Leipzig, Germany, 4289
    • Onkopraxis Probstheida
  • Lemgo, Germany, 32657
    • Klinikum Lippe Lemgo
  • Limburg, Germany, 65549
    • St Vincenz Krankenhaus
  • Lübeck, Germany, 23562
    • Lübecker Onkologische Schwerpunktpraxis
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg
  • Magdeburg, Germany, 39104
    • Gemeinschaftspraxis Haematologie und Onkologie
  • Mannheim, Germany, 68161
    • Mannheimer Onkologie Praxis
  • Marburg, Germany, 35037
    • Praxis für Innere Medizin - Hämatologie und Onkologie
  • Mutlangen, Germany, 73557
    • Stauferklinikum Schwäbisch Gmünd
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf
  • München, Germany, 80804
    • München Klinik Schwabing
  • München, Germany, 81377
    • Klinikum der Universitaet München - Grosshadern Campus
  • München, Germany, 81675
    • Klinikum rechts der Isar - Technische Universitaet Muenchen
  • Münster, Germany, 48153
    • Gemeinschaftspraxis für Hämatologie und Onkologie
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg
  • Paderborn, Germany, 33098
    • Brüderkrankenhaus St. Josef Paderborn
  • Ravensburg, Germany, 88212
    • Gemeinschaftspraxis für Hämatologie und Onkologie
  • Regensburg, Germany, 93049
    • Barmherzigen Brüder Krankenhaus
  • Regensburg, Germany, 93053
    • Schwerpunktpraxis für Hämatologie & Onkologie - OncoPro GbR
  • Rostock, Germany, 18057
    • Universitätsklinik Rostock
  • Saarbrücken, Germany, 66113
    • OnkoSaar Praxis für Hämatologie und Onkologie
  • Siegburg, Germany, 53721
    • Zentrum für abulante Hämatologie und Onkologie
  • Stuttgart, Germany, 70376
    • Robert-Bosch-Krankenhaus
  • Stuttgart, Germany, 70199
    • Marienhospital Stuttgart
  • Tübingen, Germany, 72076
    • Universitätsklinik Tübingen
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
  • Weiden, Germany, 92637
    • MVZ Weiden GmbH
  • Würzburg, Germany, 97080
    • Hämatologisch Onkologische Schwerpunktpraxis
• Ireland
  • Cork, Ireland, t12DC4A
    • Cork University Hospital
  • Dublin, Ireland, Dublin 4
    • St Vincents University Hospital
  • Dublin, Ireland, Dublin 7
    • Mater Misericordiae University Hospital
  • Dublin, Ireland, Dublin 9
    • Beaumont Hospital
  • Dublin, Ireland, Dublin 8
    • St. James's Hospital
  • Galway, Ireland, H91 YR71
    • University Hospital Galway
  • Limerick, Ireland, V94 F858
    • University Hospital Limerick
  • Waterford, Ireland, X91 ER8E
    • University Hospital Waterford
• Israel
  • Beersheba, Israel, 84101
    • Soroka University Medical Center
  • Be’er Ya‘aqov, Israel, 70300
    • Shamir Medical Center Assaf Harofeh
  • Haifa, Israel, 31048
    • Bnai-Zion Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center Ein Kerem University Hospital
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Nahariya, Israel, 22100
    • Galilee Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center Beilinson Hospital
  • Ramat Gan, Israel, 52621
    • Chaim Sheba Medical Center
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Catania, Italy, 9513
    • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
  • Ferrara, Italy, 44124
    • Azienda Ospedaliero Universitaria Di Ferrara
  • Mestre, Italy, 30174
    • Ospedale dell'Angelo
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
  • Milan, Italy, 202132
    • Irccs Ospedale San Raffaele
  • Perugia, Italy, 6123
    • Ospedale S. Maria Della Misericordia
  • Roma, Italy, 161
    • Umberto I - Policlinico di Roma - Sapienza Università
  • Roma, Italy, 168
    • Gmelli University Hospital
  • Torino, Italy, 10126
    • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223GZ
    • Jeroen Bosch Ziekenhuis
  • Alkmaar, Netherlands, 1815JD
    • Nordwest Ziekenhuisgroep, Locatie Alkmaar
  • Amsterdam, Netherlands, 1091AC
    • OLVG Amsterdam
  • Amsterdam, Netherlands, 1105AZ
    • Amsterdam Universitair Medische Centra
  • Arnhem, Netherlands, 6815AD
    • Rijnstate, Locatie Arnhem
  • Breda, Netherlands, 4818CK
    • Amphia ziekenhuis
  • Delft, Netherlands, 2625AD
    • Reinier de Graaf Ziekenhuis
  • Doetinchem, Netherlands, 7009BL
    • Slingeland Ziekenhuis
  • Dordrecht, Netherlands, 3318AT
    • Albert Schweitzer Ziekenhuis
  • Ede, Netherlands, 6716RP
    • Ziekenhuis Gelderse Vallei
  • Groningen, Netherlands, 9728NT
    • Martini Ziekenhuis
  • Harderwijk, Netherlands, 3844DG
    • Ziekenhuis St Jansdal
  • Leeuwarden, Netherlands, 8934AD
    • Medisch Centrum Leeuwarden
  • Leiderdorp, Netherlands, 2353GA
    • Alrijne Ziekenhuis
  • Nieuwegein, Netherlands, 3435CM
    • St. Antonius ziekenhuis
  • Nijmegen, Netherlands, 6532SZ
    • Canisius-Wilhelmina Ziekenhuis
  • Rotterdam, Netherlands, 3079DZ
    • Maasstad Ziekenhuis
  • Schiedam, Netherlands, 3118JH
    • Franciscus Vlietland
  • Tiel, Netherlands, 4002WP
    • Ziekenhuis Rivierenland Tiel
  • Utrecht, Netherlands, 3582 KE
    • Diakonessenhuis
  • Venlo, Netherlands, 5912BL
    • VieCuri Medish Centrum
  • Zwolle, Netherlands, 8025AB
    • Isala Zwolle
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Lørenskog, Norway, 1478
    • Akershus University Hospital
  • Oslo, Norway, 372
    • Oslo University Hospital
  • Trondheim, Norway, 7030
    • St. Olavs Hospital Trondheim University Hospital
• Spain
  • Badalona, Spain, 8916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 8035
    • Vall d'Hebron University Hospital
  • Barcelona, Spain, 8908
    • Hospital Duran i Reynals
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Málaga, Spain, 29603
    • Hospital Costa del Sol
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturias
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Marques de Valdecilla
  • Seville, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario Valencia
  • Valencia, Spain, 46026
    • Residencia Sanitaria La Fe - Valencia
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
• Sweden
  • Borås, Sweden, 50182
    • Soedra Aelvsborgs Sjukhus
  • Falun, Sweden, 79182
    • Falu Lasarett
  • Gothenburg, Sweden, 41346
    • Sahlgrenska University Hospital
  • Halmstad, Sweden, 30185
    • Hallands sjukhus Halmstad
  • Linköping, Sweden, 58185
    • Universitetssjukhuset Linköping
  • Luleå, Sweden, 97180
    • Sunderby Hospital
  • Lund, Sweden, 22185
    • Skåne University Hospital
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital Solna
  • Umeå, Sweden, 90185
    • Umea University Hospital
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital
  • Varberg, Sweden, 43281
    • Hallands Sjukhus
  • Örebro, Sweden, 70185
    • Orebro University Hospital
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
  • Baden, Switzerland, 5404
    • Kantonsspital Baden
  • Basel, Switzerland, 4031
    • Universitätsspital Basel
  • Bellinzona, Switzerland, 6500
    • Ospedale Regionale Bellinzona e Valli
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Brig, Switzerland, 3900
    • Spitalzentrum Oberwallis
  • Chur, Switzerland, 7000
    • Kantonsspital Graubunden
  • Fribourg, Switzerland, 1708
    • HFR Fribourg Hôpital cantonal
  • Geneva, Switzerland, 1211
    • Hôpitaux Universitaires Genève
  • Liestal, Switzerland, 4410
    • Kantonsspital Baselland
  • Lucerne, Switzerland, 6000
    • Luzerner Kantonsspital
  • Münsterlingen, Switzerland, 8596
    • Spital Thurgau AG - Kantonsspital Münsterlingen
  • Olten, Switzerland, 4600
    • Kantonsspital Olten
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Thun, Switzerland, 3600
    • Spital Thun
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur
  • Zurich, Switzerland, 8063
    • Stadtspital Triemli
  • Zurich, Switzerland, 8091
    • Universitätsspital Zuerich

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Documented CLL requiring treatment according to iwCLL criteria.
2. Age at least 18 years.
3. Life expectancy ≥ 6 months.
4. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.

5. 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:

   1. Absolute neutrophil count ≥ 1.0 × 109/L
   2. 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
   3. Total haemoglobin ≥ 8 g/dL (without transfusion support, unless anaemia is due to CLL)

6. 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.

7. 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.
8. 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).
9. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.

Exclusion criteria:

1. 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).
2. Transformation of CLL (Richter transformation). When Richter transformation is suspected, PET-CT and/or biopsy should be performed to rule out transformation.
3. Patients with a history of PML.
4. 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).
5. 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.
6. Uncontrolled or active infection.
7. Patients with known infection with human immunodeficiency virus (HIV).
8. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/ inducers (incl. up to 7 days prior to study treatment start).
9. 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).
10. History of stroke or intracranial hemorrhage within 6 months prior to registration for study screening.
11. Known bleeding disorders
12. Child B / C liver cirrhosis
13. Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
14. Vaccination with live vaccines 28 days prior to registration for study screening.
15. Major surgery less than 30 days before start of study treatment.
16. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
17. Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
18. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of study treatment; further pregnancy testing will be performed monthly).

19. Fertile men or women of childbearing potential unless:

    1. surgically sterile or ≥ 2 years after the onset of menopause
    2. willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment.
20. Legal incapacity.
21. Prisoners or subjects who are institutionalized by regulatory or court order.
22. Persons who are in dependence to the sponsor or an investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I (Ibrutinib); Ibrutinib p.o. will be administered until occurrence of unacceptable toxicity, progression of CLL or end of trial, whichever occurs first.	Biological: Ibrutinib; Cycles 1 - X: 420 mg daily, d1-28 p.o.; Other Names: Imbruvica
Experimental: VG (Obinutuzumab + Venetoclax); 12 cycles (q 28d): Obinutuzumab i.v. + Venetoclax p.o. will be administered for 6 cycles, followed by 6 additional cycles of Venetoclax alone	Biological: Venetoclax; 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.; Other Names: ABT-199, Venclyxto; Biological: Obinutuzumab; 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.; Other Names: GA101, Gazyvaro
Experimental: VI (Venetoclax + Ibrutinib); 15 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	Biological: Ibrutinib; Cycles 1 - X: 420 mg daily, d1-28 p.o.; Other Names: Imbruvica; Biological: Venetoclax; 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.; Other Names: ABT-199, Venclyxto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of undetectable minimal residual disease (uMRD) in peripheral blood (PB) and bone marrow (BM)	Undetectable MRD (uMRD) is defined as <10-4 (=1 CLL-cell per 10,000 leukocytes analyzed).The uMRD rate is defined as the proportion of patients having achieved uMRD.	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	MRD is defined as the number of CLL-cells that can be detected in peripheral blood (PB) or bone marrow (BM). MRD values will be categorized into negative (<10-4) and positive (≥10-4)	Up to 80 month
Overall response rate (ORR)	Proportion of patients having achieved a complete response (CR), a CR with incomplete recovery of the bone marrow (CRi), or a partial response (PR) as best response.	At final restaging (RE): 18 months after start of treatment
CR/CRi rate	Proportion of patients having achieved a CR or CRi as best response (= number of patients with best response CR or CRi divided by the number of the intention-to-treat population (ITT) population)	At final restaging (RE): 18 months after start of treatment
Incidence of safety parameters such as adverse events (AE) and adverse events of particular/special interest (AEPI/AESI)	Type, frequency, severity and relationship to study treatment.of AEs and AEPIs/AESIs	Up to 80 month
Event-free survival	Event-free survival (EFS) (I vs VG and I vs VI)	Up to 80 month
Time to next treatment	Time to next treatment (TTNT)	Up to 80 month
PFS2	Progression free survival 2 (i.e. PFS after second-line treatment)	Up to 80 month
Safety parameter TLS	Tumour lysis syndrome (TLS) risk category after G or I lead-in (before venetoclax ramp up)	Up to 80 month

Collaborators and Investigators

• Sponsor: German CLL Study Group
• Collaborators: AbbVie; Hoffmann-La Roche; Janssen Pharmaceutica N.V., Belgium; Cancer Trials Ireland; Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON); Nordic CLL Study Group (NCLLSG); Swiss Group for Clinical Cancer Research (SAKK); Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA); Grupo Español de Leucemia Linfocítica Crónica (GELLC); The Israeli CLL Study Group (ICLLSG)
• Investigators: Principal Investigator: Othman Al-Sawaf, Dr. med., German CLL Study Group

Publications and helpful links

General Publications

• 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.

Helpful Links

• Click here for more information about this study: CLL17 (German CLL Study Group)

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CLL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; venetoclax; obinutuzumab; ibrutinib
• Other Study ID Numbers: CLL17; 2019-003854-99 (EudraCT Number); 2022-500439-35-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No