A Prospective, Open-label, Multicentre, Randomized, Phase-3-trial of Acalabrutinib, Obinutuzumab and Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk Chronic Lymphatic Leukemia

• Status: Not yet recruiting
• Trial end date: 2027-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German CLL Study Group
• Collaborator: AstraZeneca
• Treatments: Acalabrutinib; Obinutuzumab; Venetoclax

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 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