therapy with ibrutinib for patients with Chronic lymphocytic leukemia with subclonal TP53 aberrations

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 185

Inclusion Criteria

1.=18 years old
2.Documented diagnosis of CLL according to International workshop on CLL (IwCLL) 2008 criteria
3.Previously untreated (steroid treatment previously administered to control autoimmune complications is allowed)
4.Negative HBsAg and negative HBcAb or positive HBcAb and negative for HBV DNA by quantitative PCR, HCV antibody negative or, in case of HCV antibody positive, HCV RNA negative
5.Progressive disease requiring treatment according to IwCLL 2008 criteria
6.Cohort 2 only: Evidence of a small (<20%) subclone carrying TP53 deletion by FISH

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 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1.Histologically documented transformation from CLL to aggressive lymphoma (Richter transformation)
2.History of stroke or intracranial hemorrhage within 6 months prior to enrollment
3.Concomitant use of warfarin or other Vitamin K antagonists
4.Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
5.Evidence of clonal TP53 mutations detected by Sanger sequencing and/or del17p in =20% of the nuclei by FISH

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To assess response to treatment in terms of overall response rate, progression-free survival and overall survival.;Primary end point(s): •TP53 mutated subclone size at WEEK 2,4,12,24,48,72,96 and yearly thereafter compared to baseline [i.e. (TP53 mutated alleles at WEEK 2,4,12,24,48,72,96 and yearly thereafter)/(TP53 mutated alleles at baseline)];Timepoint(s) of evaluation of this end point: during treatment period;Main Objective: ¿To characterize the dynamics of the clonal composition in progressive CLL patients harboring TP53 mutations detected by NGS, at different time points (Baseline, Weeks 2,4, 12,24,48,72, 96 and then every year until the end of study, at disease progression)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Overall response rate (ORR); Progression-free survival (PFS); Overall survival (OS);Timepoint(s) of evaluation of this end point: during treatment and follow up period; during treatment and follow up period; during treatment and follow up period

Related Trials