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

Prior treatment

• 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

Other illness

• 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

Other

• Transformation of CLL (Richter transformation)
• Pregnant women and nursing mothers

• 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