Chronic Lymphocytic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864
Conditions
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Documented CLL or SLL requiring treatment according to IWCLL criteria after either being refractory to first line therapy or relapse after initial therapy. • Age at least 18 years. • Adequate bone marrow function defined as: - Absolute neutrophil count (ANC) >0.75 x 10^9/L - Platelet count >30,000 /µL 30 x 10^9/L. - Hemoglobin >8.0 g/dL (5 mmol/L) Unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy • Creatinine clearance (CrCL) = 30ml/min . • Adequate liver function as indicated - AST or ALT= 3.0 x ULN - Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) -Prothrombin time (PT)/International normal ratio (INR) =65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: • Any prior therapy with ibrutinib and/or venetoclax. • Transformation of CLL (Richter’s transformation). • Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML). • Malignancies other than CLL currently requiring systemic therapies or not being treated in curative intention before or showing signs of progression after curative treatment. • Known allergy to xanthine oxidase inhibitors and/or rasburicase. • Known bleeding disorders (e.g., von Willebrand’s disease or hemophilia). • Uncontrolled or active infection. •Patients requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists. • History of stroke or intracranial hemorrhage within 6 months prior to randomization. • Major surgery within 28 days prior to registration. • Use of investigational agents which might interfere with the study drug within 28 days prior to registration. • Vaccination with live vaccines within 28 days prior to registration • Steroid therapy within 7 days prior to registration, with the exception of inhaled steroids for asthma, topical steroids, steroids up to 25 mg of prednisolone daily to control autoimmune phenomenon’s, or replacement/stress corticosteroids. • Pregnant women and nursing mothers. • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Evaluate efficacy of ibrutinib + venetoclax (VI) in terms of proportion of patients fulfilling the criteria for progression free survival (PFS) at 12 months after stopping therapy (27 months after starting treatment) for patients randomized to stop treatment (arm B of the study), reinitiated treatment due to MRD positivity not considered progression ;Secondary Objective: - Evaluation of the efficacy in terms of minimal residual disease (MRD) at 12 months after stopping treatment (month 27) - Evaluation of efficacy in terms of PFS (IWCLL criteria) - Time to and number of patients reinitiating treatment - Time to treatment failure after reinitiated treatment - Time to next CLL treatment, - MRD after cycle 12 (PB) and 15 (PB and BM) and at later time points in PB, - Overall Survival (OS), - Complete response (CR)/ Partial Response (PR)/ Stable disease (SD) after cycle 3, 9, 12, 15, and at month 27 and month 51 (3 years after stopping treatment) - Duration of response – To evaluate safety with regards to type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment. – To evaluate patient related outcomes, measured in terms of health-related quality of life (QoL) by EORTC QLQ-C30 and QLQ-CLL16 questionnaires. ;Primary end point(s): • Proportion of patients fulfilling the criteria for progression free survival (PFS) at 12 months after stopping therapy (27 months after starting treatment) for patients randomized to stop treatment. In this trial, reinitiated treatment due to MRD positivity will not be considered as progression, and symptomatic CLL according to IWCLL criteria within 12 months after randomization followed by reinitiation treatment resulting in a response (at least SD) before or at 12 months after randomization will neither be considered as progression.;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated when data of all pat | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Minimal residual disease (MRD) at 12 months after stopping treatment (month 27) for patients randomized to stop of treatment. • PFS of all study groups. • Time to and number of patients reinitiating treatment • Time to treatment failure after reinitiated treatment • Time to next CLL treatment • MRD after cycle 12 (PB) and 15 (PB and BM) and at later time points in PB • Overall survival (OS) • Complete response (CR)/ Partial Response (PR)/ Stable disease (SD) after cycle 3, 9, 12, 15 and month 27 and month 51 (3 years after stopping treatment) • Duration of response • Safety parameters: Type, frequency, and severity of - adverse events (AEs) and - adverse events of special interest (AESI) and their relationship to study treatment • Health-related quality of life (QoL) by EORTC QLQ-C30 and QLQ-CLL16 questionnaires • Exploratory endpoints: • Evaluation of relationship between various baseline markers and clinical outcome parameters • Various markers at time of progression • Correlation between MRD in BM and PB • Correlation between MRD in BM and PFS/OS • Correlation between MRD in PB and PFS/OS ;Timepoint(s) of evaluation of this end point: Endpoints will be evaluated when relevant data of all patients are available | — |
Countries
Belgium, Denmark, Finland, Netherlands, Norway, Sweden
Contacts
Public ContactHOVON Data Center
Erasmus MC -Clinical Trial Center
Outcome results
None listed