Short-term Combined Acalabrutinib and Venetoclax Treatment of Newly Diagnosed Patients With CLL at High Risk of Infection and/or Early Treatment, Who do Not Fulfil IWCLL Treatment Criteria.
Many patients with CLL have a weakened immune system due to their disease. It increases their risk of developing serious, treatment-requiring infections such as blood poisoning or pneumonia, which in the worst case may end with fatal outcomes. Serious infections due to CLL are responsible for one third of all deaths among CLL patients. PreVent-ACaLL study will investigate whether a combination of two known types of cancer drugs can reduce the risk of infection and thus mortality when given preventively to newly diagnosed CLL patients. A newly developed register-based computer model can predict which patients are at high risk in order to develop infections as a result of their CLL. A preventive treatment might be initiated before patients need chemotherapy. In this way, the cancer disease might be reset so that the immune system, which is inhibited by CLL, is restored and the risk of fatal infections is minimized.
• CLL diagnosed according to IWCLL criteria within one year prior to randomization
• High risk of infection and/or progressive treatment within 2 years according to CLL-TIM
• IWCLL treatment indication not fulfilled
• Life expectancy \> 2 years
• Age at least 18 years
• Ability and willingness to provide written informed consent and adhere to study procedures and treatment
• Adequate bone marrow function as indicated by platelets above 100 x 10E9, hemoglobin above 10 g/dL and neutrophils above 1 x 10E9
• Creatinine clearance above 30 mL/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault
• 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 serological 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), negative testing for hepatitis C RNA within 6 weeks prior to registration.
⁃ Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.
⁃ Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of investigational drugs.
⁃ Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
⁃ Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information