Identification of Biomarkers That Are Predictive of Early Ibrutinib Treatment Failure in High Risk TP53 Mutated Chronic Lymphocytic Leukemia

NCT02827617 | Completed

• 1 other identifier: IOSI-EMA-001
• Study Type: observational
• Target: 56
• Locations: 2 countries
• Sites: 13

Brief Summary

The general aim of the project is the identification of dynamic molecular markers that can help the early and real time prediction of sustained benefit or no benefit from ibrutinib treatment in CLL harboring TP53 mutations. Specific aims of the project include: 1) Assess whether clearance of TP53 mutated clones translates into a predictive biomarker of long term benefit from ibrutinib treatment in CLL. 2) Assess whether plasma cell free DNA represents a sensitive tool that can early and dynamically inform on the development of ibrutinib resistant mutations in CLL.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Ibrutinib; TP53; Chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (1)

• Impact of clonal response on PFS

  To evaluate the impact of clonal response (namely clearance of TP53 mutated alleles in the peripheral blood (PB) CLL cells at Week 24 after treatment start) on PFS measured according to iwCLL guidelines (Hallek 2008) as the interval from ibrutinib treatment start to progression (event), death (event) or last follow-up (censoring). Progression will be defined as per investigator assessment.

  2/2016-2/2021

Secondary Outcomes (9)

• Proportion of clonal response at Week 24 after treatment start

  2/2016-2/2021

• Cumulative proportion of clonal response

  2/2016-2/2021

• Impact of clonal response on overall survival

  2/2016-2/2021

• Effect of clonal response on the cumulative incidence of acquisition of resistance-mutations

  2/2016-2/2021

• Effect clonal response on the cumulative incidence of transformation to Richter syndrome

  2/2016-2/2021

Study Arms (1)

TP53 mutated CLL

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Treatment with ibrutinib 420 mg quaque die in the clinical practice

Also known as: PCI-32765

TP53 mutated CLL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult CLL patients harboring TP53 genetic abnormalities, independent of whether treatment naïve or previously treated, who warrants treatment according to iwCLL 2008 criteria, and who is planned to receive ibrutinib at standard dose as per clinical practice

You may qualify if:

• Male or female adults 18 years or older
• Documented diagnosis of CLL, according to iwCLL 2008 criteria
• Presence of TP53 mutation as demonstrated by sequencing at the local laboratory and/or presence of 17p deletion as demonstrated by fluorescence in situ hybridization (FISH) testing performed at the local laboratory
• CLL that warrants treatment
• Planned treatment with ibrutinib 420 mg quaque die
• Willing and able to comply with scheduled visits, laboratory tests, and study procedures
• Evidence of a signed informed consent

You may not qualify if:

• Current or prior histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation).
• Prior treatment with ibrutinib or idelalisib

Sponsors & Collaborators

• Oncology Institute of Southern Switzerland: lead

Study Sites (13)

Onco Ematologia Clinico Sperimentale, I.R.C.C.S. Centro di Riferimento Oncologico

Aviano, 33081, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Dipartimento di Ematologia, Niguarda Cancer Center, Ospedale Niguarda

Milan, 20133, Italy

Location

Department of Medical and Surgical Sciences, section of Hematology

Modena, 41124, Italy

Location

Divisione di Ematologia, Universita' del Piemonte Orientale

Novara, 28100, Italy

Location

Institute of Hematology, Catholic University S. Cuore

Roma, 00168, Italy

Location

Department of Haematology, Tor Vergata Hospital

Rome, 00133, Italy

Location

Clinica Ematologica, Centro Trapianti e Terapie Cellulari "Carlo Melzi"

Udine, 33100, Italy

Location

Ematologia, Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Oncology Institute of Southern Switzerland

Bellinzona, Switzerland, 6500, Switzerland

Location

Division of Hematology, Department of Internal Medicine, Basel University Hospital

Basel, 4031, Switzerland

Location

Hematology, Luzern Kantonsspital

Lucerne, 6000, Switzerland

Location

Clinica Luganese Moncucco

Lugano, 6903, Switzerland

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tumor periphral blood cells, Plasma, Tumor genomic DNA, Plasma cell free DNA

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Davide Rossi, MD, PhD

  Oncology Institute of Southern Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 11, 2016
• Study Start: June 1, 2016
• Primary Completion: August 31, 2021
• Study Completion: May 16, 2024
• Last Updated: November 18, 2025

Record last verified: 2025-11

Locations

IT (9); CH (4)