STop and restart Acalabrutinib In fRail patients with previously untreated CLL(STAIR)

Phase 1

• Conditions: Chronic lymphoid leukemia; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-006081-36-FR
• Lead Sponsor: FILO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-04
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

•Age>70 years or older
•ECOG performance status < 2
•Previously untreated CLL or SLL
•CLL or SLL requiring treatment according to the IWCLL 2018 criteria2
•Total CIRS score >6 or 30 •Both patients with or without TP53 disruption (deletion del 17p and or TP53) can be included
•Patients can be included whatever their IGHV mutational status
•Patients with therapy-controlled cardiovascular comorbidities and/or anticoagulation (novel oral anticoagulant alone, aspirin alone, heparin alone) can be included (patients treated by vitamin K antagonist or dual anti-platelet therapy cannot be included)
•Life expectancy > 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 <1.5, aspartate transaminase and alanine transaminase =3 the institutional upper limits of normal values, unless directly attributable to CLL
•Signed (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including specify biology analysis, and are willing to participate in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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)<br>•Quality of life<br>•Tolerance profil<br>•Overall response to re-treatment with ACALABRUTINIB after discontinuation in the experimental arm.<br>;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