RECRUITING Phase 3 ClinicalTrials.gov

A Phase-3-trial of Acalabrutinib, Obinutuzumab & Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk CLL

Sponsor: German CLL Study Group • ClinicalTrials.gov ID: NCT05197192

Registry updated: 2026-08-20

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Description

This multicenter, prospective, open-label, randomized, superiority phase 3 study is designed to demonstrate that treatment with a triple combination of acalabrutinib, obinutuzumab and venetoclax (GAVe) prolong the progression-free survival (PFS) as compared to treatment with the combination of obinutuzumab and venetoclax (GVe) in pa-tients with high risk CLL (defined as having at least one of the follow-ing risk factors: 17p-deletion, TP53-mutation, complex karyotype or an unmutated IGHV-gene status).

Interventions

Obinutuzumab (Drug)
Obinutuzumab i.v. infusion: Cycle 1 Day 1: Obinutuzumab 100 mg i.v. Cycle 1 Day 1 (or 2): Obinutuzumab 900 mg i.v. Cycle 1 Day 8: Obinutuzumab 1000 mg i.v. Cycle 1 Day 15: Obinutuzumab 1000 mg i.v. Cycles 2-6: Day 1: Obinutuzumab 1000 mg i.v.
Venetoclax (Drug)
Venetoclax p.o.: Cycle 1: Days 22-28: Venetoclax 20 mg (2 x 10 mg) Cycle 2: Days 1-7: Venetoclax 50 mg (1 x 50 mg) Cycle 2:Days 8-14: Venetoclax 100 mg (1 x 100 mg) Cycle 2:Days: 15-21: Venetoclax 200 mg (2 x 100 mg) Cycle 2:Days: 22-28: Venetoclax 400 mg (4 x 100 mg) Cycles 3-12: Days 1-28: Venetoclax 400 mg (4 x 100 mg)
Acalabrutinib (Drug)
Cycles 15-24: Days 1-28: 100 mg acalabrutinib twice daily p.o. approx. every 12 hrs (corresponding to a total daily dose of 200 mg).

Eligibility criteria

Inclusion Criteria: * Documented CLL/SLL requiring treatment according to iwCLL criteria * Age at least 18 years * At least one of the following risk factors: 17p-deletion, TP53-mutation, complex karyotype (defined as defined as the presence of 3 or more chromosomal aberrations in 2 or more metaphases) or an unmutated IGHV gene status. * Life expectancy ≥ six months * Adequate bone marrow function indicated by a platelet count \>30 x10\^9/l * Creatinine clearance ≥ 30ml/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 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 until 12 months after last treatment cycle),or hepatitis C (negative testing for hepatitis C RNA within 6 wee * ks prior to registration for study screening (i.e. PCR only required when serology was positive)) * ECOG (Eastern Cooperative Oncology Group Performance Status) status 0-2 Exclusion Criteria: * 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) * Absence of high risk disease (17p-deletion, TP53-mutation complex karyotype * An individual organ/system impairment score of 4 as assessed by the CIRS definition (e.g. advanced cardiac disease (NYHA class 3 or 4) 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) * Transformation of CLL (Richter transformation) * Malignancies other than CLL currently requiring systemic therapies * Uncontrolled or active infection of HIV/PML or any other active infection * Anticoagulant therapy with warfarin or phenoprocoumon * Pregnant women and nursing mothers

Conditions

Chronic Lymphocytic Leukemia

Locations

Helios Klinikum Bad Saarow — Bad Saarow, Germany
DRK Kliniken Berlin Köpenick — Berlin, Germany
Ev. Diakoniekrankenhaus — Bremen, Germany
Universitätsklinik Köln — Cologne, Germany
St. Johannes Hospital — Dortmund, Germany
Marien Hospital Düsseldorf — Düsseldorf, Germany
St. Antonius-Hospital — Eschweiler, Germany
Universitaetsklinikum Essen — Essen, Germany
Katholisches Krankenhaus Hagen - St. Josefs Hospital — Hagen, Germany
Universitaetskliniken des Saarlandes — Homburg, Germany
Klinikum Idar-Oberstein SHG — Idar-Oberstein, Germany
Staedtisches Klinikum Karlsruhe — Karlsruhe, Germany
Universitaetsklinikum Schleswig-Holstein Campus Kiel — Kiel, Germany
Klinikum Landshut — Landshut, Germany
Klinikum Lippe-Lemgo — Lemgo, Germany
St Vincenz Krankenhaus — Limburg, Germany
Universitaetsklinikum Magdeburg — Magdeburg, Germany
Klinikum Hochsauerland - St. Walburga Krankenhaus — Meschede, Germany
KH Kliniken Maria Hilf — Mönchengladbach, Germany
Krankenhaus Muenchen-Schwabing — Munich, Germany
Klinikum Rechts der Isar - Technische Universitaet Muenchen — Munich, Germany
Kliniken Ostalb, Stauferklinikum Schwäbisch Gmünd — Mutlangen, Germany
Klinikum Oldenburg — Oldenburg, Germany
Brüderkrankenhaus St. Josef Paderborn — Paderborn, Germany
Universitätsklinik Rostock — Rostock, Germany
Caritas-Klinik St. Theresia — Saarbrücken, Germany
Klinikum Sindelfingen-Böbingen — Sindelfingen, Germany
Marienhospital Stuttgart — Stuttgart, Germany
Universitaetsklinik Tuebingen — Tübingen, Germany
Universitätsklinik Ulm — Ulm, Germany

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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