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

Clonal evolution in progressive CLL patients harboring subclonal TP53 aberrations treated with ibrutinib first-line - CLOSE (PS-CLL-001)

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-001099-49-IT

Enrollment

185

Registered

2021-06-01

Start date

2018-07-12

Completion date

Unknown

Last updated

2024-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Lymphocytic Leukemia (CLL) MedDRA version: 21.0 Level: LLT Classification code 10008956 Term: Chronic lymphatic leukaemia System Organ Class: 100000004864

Interventions

Product Name: ibrutinib Product Code: [PCI-32765] Pharmaceutical Form: Capsule, hard INN or Proposed INN: IBRUTINIB CAS Number: 936563-96-1 Current Sponsor code: NA Concentration unit: mg milligram(s)

Eligibility

Sex/Gender

All

Inclusion criteria

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

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
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 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	—

Measure

Time frame

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 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

—

Secondary

Measure	Time frame
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	—

Countries

Italy, Switzerland

Contacts

Public ContactUfficio Data Management

Ospedale San Raffaele

scarano.eloise@hsr.it00390226433919

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026