REfractorinesS to Ibrutinib BTKi and Systemic Targeted Therapy (RESIST)

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

Study Overview

• Status: Completed
• Conditions: Small Lymphocytic Leukemia; CLL, Relapsed; CLL, Refractory; Bruton Tyrosine Kinase Inhibitor

• Study Type: Observational
• Enrollment (Actual): 152

Contacts and Locations

• Study Contact: Name: Valérie ROUILLE; Phone Number: +33 0247391896; Email: v.rouille@filo-leucemie.org
• Study Contact Backup: Name: Marie POINSIGNON-BLANCARD; Phone Number: +33 0247391896; Email: m.poinsignon-blancard@filo-leucemie.org

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • CHU Estaing - Hématologie Clinique Adulte
  • Lyon, France, 69373
    • Centre Léon Bérard - Hématologie
  • Marseille, France, 13273
    • Institut Paoli-Calmettes - Hématologie Clinique
  • Montpellier, France, 34295
    • MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique
  • Pessac, France, 33604
    • Bordeaux Pessac
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Strasbourg, France, 67033
    • Strasbourg - Icans
  • Toulouse, France, 31059
    • Toulouse - IUCT Oncopole - Service d'Hématologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: French Innovative Leukemia Organisation
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Loïc YSEBAERT, French Innovative Leukemia Organisation

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 17, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Leukemia, Lymphoid
• Other Study ID Numbers: FILObsLLC_RESIST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No