bloodcancer Chronic Lymphocytic Leukemia
Conditions
Interventions
In the study treatment group, subjects will be treated with a combination of
the drugs acalabrutinib and venetoclax. The treatment will be started within 14
days after they have been randomised. The
Sponsors
Rigshospitalet/Copenhagen University hospital
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. CLL diagnosed according to IWCLL criteria within one year prior to randomization 2. High risk of infection and/or progressive treatment within 2 years according to CLL-TIM 3. IWCLL treatment indication not fulfilled 4. Life expectancy > 2 years 5. Age at least 18 years 6. Ability and willingness to provide written informed consent and adhere to study procedures and treatment 7. Adequate bone marrow function as indicated by platelets above 100 x 10E9, hemoglobin above 10 g/dL and neutrophils above 1 x 10E9 8. Creatinine clearance above 30 mL/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault 9. Adequate liver function as indicated by a total bilirubin
Exclusion criteria
Exclusion criteria: 1. Prior CLL treatment (including monoclonal antibodies, chemotherapy, small molecules, including CD20 antibodies, BTK inhibitors and bcl-2 inhibitors for any indication) 2. Transformation of CLL (Richter*s transformation) 3. Previous autoimmune disease as AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura) treated with immune suppression or uncontrolled AIHA or ITP 4. History of progressive multifocal leukoencephalopathy 5. HIV infection (a negative test required) 6. Known active infection 7. Malignancies other than CLL requiring systemic therapies (except anti-hormonal therapies) or considered to impact survival 8. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers or anticoagulant therapy with vitamin K antagonists 9. History of bleeding disorders or current platelet inhibitors or anticoagulant therapy 10. History of clinically significant cardiovascular disease such as arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec at screening. 11. History of stroke or intracranial hemorrhage within 6 months prior to registration. 12. Use of investigational agents which might interfere with the study drug within 28 days prior to registration. 13. Vaccination with live vaccines within 28 days prior to registration. 14. Major surgery less than 30 days before start of treatment. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug. 15. Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial. 16. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly). 17. Fertile men or women of childbearing potential unless: surgically sterile or >= 2 years after the onset of menopause or willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index 2x ULN. 23. Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Grade >=3-Infection-free survival in the treatment arm compared to the observation arm 12 weeks after finishing treatment, (24 weeks after treatment initiation). This is a non-inferiority analysis as detailed in the statistical analysis plan to assure safety of the combination treatment in this preemptive trial population. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Grade >=3-infection free and CLL-treatment-free survival at end of treatment, 1 year and 2 years after enrollment • Rate of overall survival (OS) and cause of death • Treatment free survival • Rate and CTCAE V5.0 grade of infections • Response rate and duration according to IWCLL criteria • Treatment related adverse events, type, frequency and severity during and for 2 years after treatment • Immune function as assessed by immune phenotyping, functional TruCulture assays and measurements of cytokine levels | — |
Countries
Netherlands
Outcome results
None listed