Chronic Lymphocytic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Venclyxto
Product Name: Venetoclax 10 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: VENETOCLAX
CAS Number: 1257044-40-8
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Rigshopitalet/Copenhagen University Hospital
Eligibility
Sex/Gender
All
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= 2 x, AST or ALT = 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome. 10. 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. 11. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2. 12. Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 30 days after the last dose of investigational drugs. 13. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. 14. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 170
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 is 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 (eg, 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 |
|---|---|
| Main Objective: Primary Objective phase 2 part: 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. Primary Objective optional phase 3 part: Grade =3-infection free and CLL-treatment-free survival 2 years after enrollment ;Secondary Objective: Secondary Objectives: - 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 Exploratory Objectives: - MRD levels in bone marrow and peripheral blood - Quality of life during and for 2 years after treatment, QLQC30 and CLL17 ;Primary end point(s): Grade =3-Infection-free survival in the treatment arm compared to the observation;Timepoint(s) of evaluation of this end point: 24 weeks after treatment initiation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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 ;Timepoint(s) of evaluation of this end point: End of treatment, 1 and 2 years after enrolment and continuously as rate | — |
Countries
Denmark, Netherlands, Sweden
Contacts
Public ContactPrincipal Investigator
Rigshopitalet/Copenhagen University Hospital
Outcome results
None listed