REfractorinesS to Ibrutinib BTKi and Systemic Targeted Therapy

Study Overview
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Brief Summary
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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

Official Title
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REfractorinesS to Ibrutinib BTKi and Systemic Targeted Therapy

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

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Full population<br>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<br>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?
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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 |