Compares acalabrutinib added to two drugs in untreated high-risk leukemia

Trial details

Who runs it

German CLL Study Group

Trial code

NCT05197192EU 2023-506414-46-00

Record updated

20 August 2026

Original 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).Read full original descriptionShow less

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 Chronic Lymphocytic Leukemia (CLL)

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).

Inclusion: 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: 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); Anticoagulant therapy with warfarin or phenoprocoumon; 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); Malignancies other than CLL currently requiring systemic therapies; Uncontrolled or active infection of HIV/PML or any other active infection; Transformation of CLL (Richter transformation); Pregnant women and nursing mothers.

ClinicalTrials.gov NCT05197192 · EU CTIS 2023-506414-46-00