REfractorinesS to Ibrutinib BTKi and Systemic Targeted Therapy

NCT05621148 | Completed

• 1 other identifier: FILObsLLC_RESIST
• Study Type: observational
• Target: 152
• Locations: 1 country
• Sites: 8

Brief Summary

Data evaluating and quantifying real-world outcomes of patients post-ibrutinib discontinuation, as well as outcomes of patients who have progressed on a Bruton tyrosine kinases inhibitors (BTKi) and received prior venetoclax are very limited. There are no robust studies specifically designed to assess outcomes of patients with chronic lymphocytic leukemia (CLL) receiving third line or subsequent treatments. As such, there is no established standard of care for these multiple Relapsed/Refractory (RR) patients. Furthermore, despite new oral agents approved in third-line RR CLL, there are limited published data on how to best sequence these agents and how to manage patients who fail these therapies. As the best salvage therapy in patients who fail all available oral these agents is unknown, this is a population of patients with unmet medical need. The aim of this study is to determine unmet need and treatment patterns of data from two types of populations, all previously exposed to ibrutinib (or other BTKi) for the full patient population and both ibrutinib (or other BTKi and venetoclax) for the narrow patient population, where these agents failed these subcategories of patient populations, at least in 3rd line therapy (in other words, having at least received two lines of therapy before)

• Patients with prior treatment with BTKi (full patient population) - Underlying tenet: these patients have been treated with a BTKi in at least one of two or more prior lines of therapy and progressed - FULL POPULATION
• Patients who progressed BTKi and failed VEN (defined as patients who discontinued venetoclax (VEN) due to disease progression, intolerability, or failure to achieve an objective response within 3 months of initiating therapy; small patient population) - Tenet: these patients have been treated with both BTKi and VEN in any one of the prior two lines of therapy and progressed. - NARROW POPULATION

Conditions

CLL, Relapsed; CLL, Refractory; Bruton Tyrosine Kinase Inhibitor; Small Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Response rate of treatment patterns in patients with CLL

  Overall response rate (complete, partial, stable) for each treatment received

  from BTKi initiation until progression/failure at Venetoclax treatment, assessed up to 7 years

Study Arms (2)

Full population

LLC patients with prior treatment with BTKi - Underlying tenet: these patients have been treated with a BTKi in at least one of two or more prior lines of therapy and progressed - FULL POPULATION

Narrow population

LLC Patients who progressed BTKi and failed VEN (defined as patients who discontinued VEN due to disease progression, intolerability, or failure to achieve an objective response within 3 months of initiating therapy; small patient population) - Tenet: these patients have been treated with both BTKi and VEN in any one of the prior two lines of therapy and progressed

Eligibility Criteria

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

Study Population

Patients previously exposed to ibrutinib (or other BTKi) : treatment with a BTKi in at least one of two or more prior lines of therapy and progressed

You may qualify if:

• Documented diagnosis of CLL or small lymphocytic leukemia (SLL).
• ≥ 18 years of age the time of initial diagnosis.
• Venetoclax therapy in at least third line of treatment (LOT) during the period considered, following at least one LOT with BTKi
• Patients who received VEN during prior LOTs are eligible.
• Patient not opposed to data collection (including deceased patients)

You may not qualify if:

• Exposure to cellular therapy, including CAR T-cells / Allo-Stem Cell Transplantation.
• Richter's transformation.

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Bristol-Myers Squibb: collaborator

Study Sites (8)

CHU Estaing - Hématologie Clinique Adulte

Clermont-Ferrand, 63000, France

Location

Centre Léon Bérard - Hématologie

Lyon, 69373, France

Location

Institut Paoli-Calmettes - Hématologie Clinique

Marseille, 13273, France

Location

MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, 34295, France

Location

Bordeaux Pessac

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Strasbourg - Icans

Strasbourg, 67033, France

Location

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Loïc YSEBAERT

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 28, 2022
• First Posted: November 17, 2022
• Study Start: January 25, 2023
• Primary Completion: December 31, 2023
• Study Completion: March 31, 2024
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)