Chronic lymphoid leukemia
Conditions
Interventions
Trade Name: CALQUENCE
Product Name: ACALABRUTINIB
Pharmaceutical Form: Capsule
Sponsors
FILO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age>70 years or older • ECOG performance status 6 or 30 6 months • Adequate hematology values: absolute neutrophil count = 0.75 x 109/L, platelet count = 50 x 109/L. • Adequate liver function as indicated by a total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
Exclusion criteria: • Known HIV seropositivity • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: ? *Uncontrolled and/or active systemic infection (viral, bacterial or fungal) ? ? *Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are on ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment a. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus PCR result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded. b. Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enrollment. Those who are hepatitis C virus PCR positive will be excluded ? *Active and uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) (isolated positive DAT is not an exclusion criteria) and idiopathic thrombocytopenic purpura (ITP). ? *Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. • Patients treated by vitamin K antagonist or dual anti-platelet therapy • History of bleeding diathesis (e.g. hemophilia or von Willebrand disease) • History of confirmed progressive multifocal leukoencephalopathy (PML). • Concurrent severe diseases which exclude the administration of therapy : ? *heart insufficiency NYHA grade III/IV, LEVF < 50% and or RF < 30%, myocardial infarction within the past 6 months prior to study ? *Significant cardiovascular disease such as symptomatic 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 ( Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study) ? *severe chronic obstructive lung disease with hypoxemia ? *history of stroke or intra-cranial hemorrhage within the last 6 months ? *severe diabetes mellitus ? *uncontrolled hypertension ? *impaired renal function with creatinine clearance < 30 ml/min according the formula of Cockroft and Gault • Patient who 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 in this study. • Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection) • Evidence for Richter syndrome • Treatment with any of the following within 7 days prior to the first dose of study drug: ? steroid therapy for anti-neoplastic intent. • A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the patient’s participation in this study or interpretation of study outcomes • Major surgery within 30 days prior to the first dose of study treatment. • History of prior other malignancy that could affect compliance with the protocol or interpretation of resu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine whether discontinuating ACALABRUTINIB after 18 months in treatment-naïve CLL patients affects progression-free survival (PFS) at one year after treatment interruption.;Secondary Objective: •The impact of ACALABRUTINIB withdrawal on Time to next treatment (TTNT) and overall survival (OS) •Quality of life •Tolerance profil •Overall response to re-treatment with ACALABRUTINIB after discontinuation in the experimental arm. ;Primary end point(s): PFS (Progression free survival) at one year post-ACALABRUTINIB discontinuation is defined as the time from randomization (M19) to progression (needing therapy or not) or death from any cause. Patients alive and progression-free will be censored at the last disease assessment or at initiation of next treatment. Progression will be evaluated using iwCLL2018 criteria;Timepoint(s) of evaluation of this end point: one year post end of acalabrutinib | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • OS is defined as the time from randomization (M19) to death from any cause. Patients alive will be censored at last follow-up news. • TTNT is defined as the time from randomization (M19) to initiation of next treatment required for symptomatic CLL. Patients without initiation of next treatment will be censored at last follow-up date. This need for restarting therapy will be centrally validated by an independent board review and based on iwCLL 2018 criteria for symptomatic CLL.. • Overall Response Rate (ORR) to re-treatment is defined as the proportion of re-treated patients who achieved best response of complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) per iwCLL 2008 criteria. • QoL will be evaluated using the EORTC QLQ-C30 questionnaire • Safety and tolerability of ACA will be assessed using the NCI-CTCAE v.5;Timepoint(s) of evaluation of this end point: - at month 18 or at time end of treatment - progression - death - at months 12, 18, 21, 24, 27, 30 then every 6 months for QoL - safety during all the study | — |
Countries
France
Contacts
Public ContactDelphine NOLLET
FILO
Outcome results
None listed