A Prospective, Open-label, Multicentre, Randomized, Phase-3-trial of Acalabrutinib, Obinutuzumab and Venetoclax (GAVE) Compared to Obinutuzumab and Venetoclax (GVE) in Previously Untreated Patients With High Risk (17P-deletion, TP53-mutation or Complex Karyotype) Chronic Lymphatic Leukemia (CLL)

CLL16

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 or complex karyotype).

2022-04-19

2026-05-01

2027-02-01

Recruiting

Early phase I

650

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 or complex karyotype (defined as defined as the presence of 3 or more chromosomal aberrations in 2 or more metaphases.). * 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 650, 'type': 'ESTIMATED'}}

2024-03-25