Study on Treatment Outcome Patterns for Patients With CLL After Discontinuation of BTK Inhibitors

Phase 2Not Yet RecruitingNCT07526597

UNC Lineberger Comprehensive Cancer Center45 enrolled

Overview

This Phase II hybrid decentralized multicenter study examines the outcomes of stopping Bruton tyrosine kinase inhibitor (BTKi) therapy in patients with chronic lymphocytic leukemia (CLL) who have remained in remission for at least two years. The primary objective is to determine how long patients remain free from disease progression or death after discontinuing treatment, measured as event free survival. The study also evaluates whether stopping BTKi therapy leads to improvements in quality of life and reductions in treatment related side effects. Researchers will follow patients over time to assess if the cancer returns, whether resistance to therapy develops, and how patients feel during the treatment free period. In addition, the trial will investigate how discontinuing BTKi therapy affects immune function, including whether immune recovery occurs and infection risk decreases. Preliminary data indicate that patients may experience a treatment free interval exceeding two years after stopping therapy, with associated improvements in quality of life. By prospectively evaluating a time limited treatment strategy, this trial aims to determine whether durable disease control can be maintained off therapy while also assessing the resolution of BTKi related adverse events and changes in patient reported outcomes. Overall, the study seeks to determine whether patients can safely discontinue BTKi therapy and potentially restart treatment later if needed, thereby maintaining disease control while reducing the burden of continuous therapy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Lymphocytic Leukemia

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: In order to participate in this study a subject must meet all of the eligibility criteria outlined below. * Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. * Subjects is willing and able to comply with study procedures based on the judgement of the investigator. * Age ≥ 18 years at the time of consent. * Eastern Cooperative Oncology Group Performance Status of 0-3 or Karnofsky Performance Status of ≥40 * Confirmed of a diagnosis of CLL (Chronic Lymphocytic Leukemia) or SLL (Small Lymphocytic Lymphoma) according to International Workshop on Chronic Lymphocytic Leukemia 2018 Guidelines at any point prior to study enrollment. * At the time of enrollment, patients must be receiving treatment with a covalent Bruton tyrosine kinase inhibitor in the first or second line setting and have been receiving this treatment for at a minimum 2 years. Patients may have previously received anti-CD20 monoclonal antibodies (such as rituximab or obinutuzumab) in combination with the cBTKi. Exclusion Criteria: * Patients must not have evidence of progressive CLL as defined by IWCLL 2018 criteria. * Participants with history of malignancy other than CLL/SLL are allowed

Outcomes

Primary Outcomes

Event-free survival (EFS)

EFS will be defined as the proportion of patients who remain alive, do not meet International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for initiation of next chronic lymphocytic leukemia (CLL) therapy, and have not started a new CLL - directed treatment.

Time frame: 2 years

Secondary Outcomes

Progression Free Survival (PFS)

Progression Free Survival (PFS) will be defined as the proportion of patients who remain alive, free of relapse from complete response or partial response, free of progression of chronic lymphocytic leukemia (CLL), and have not started a new CLL treatment at 2 years after discontinuation of Bruton tyrosine kinase inhibitors (BTKi).

Time frame: 2 years

Overall Survival (OS)

Overall Survival (OS) will be defined as the proportion of patients who remain alive after discontinuation of Bruton tyrosine kinase inhibitors (BTKi).

Time frame: Up to 60 months

Time to initial detection of measurable residual disease (MRD)

Time to initial detection of measurable residual disease (MRD) or clinical evidence of progression will respectively be defined as the time from discontinuation of BTKi to initial detection of MRD (via flow cytometry) or progression of CLL that meets IWCLL criteria and/or treating physician requirement for initiation of next CLL therapy.

Time frame: Up to 60 months

Overall and complete response rates

Overall and complete response rates will be defined as the percentage of patients who respectively achieve overall and complete response to next CLL therapy, based on IWCLL criteria.

Time frame: 2 years

Rate of resolution of BTKi-related adverse events

Rate of resolution of BTKi-related adverse events will be defined as the percentage of patients whose adverse events attributed to BTKi treatment have improved, subsided, or completely disappeared after discontinuation of BTKi, to the extent that the patient's condition returns to baseline or to a clinically acceptable grade (typically Grade ≤ 1 per CTCAE) as graded by NCI CTCAE v5.0 and Quality of Life assessments.

Time frame: 2 years

Incidence of new infections

Incidence of new infections will be defined as the percentage of patients who respectively have new infections after discontinuation of BTKi

Time frame: 1 year

Incidence of second cancers

Incidence of second cancers will be defined as the percentage of patients who respectively have second cancers after discontinuation of BTKi.

Time frame: 5 years

Association between biomarkers and disease outcomes

Association between biomarkers and disease outcomes as defined by EFS, PFS, OS, PFS, duration of response, duration of MRD undetectable disease state, and Richter's transformation (transforms into a fast-growing lymphoma).

Time frame: 5 years

Change in Total Score of Functional Assessment of Cancer Therapy (FACT) -Leukemia

Change in FACT -Leukemia Total Score from prior to discontinuation of BTKi to 6 months after discontinuation of BTKi. The FACT-Leukemia is a patient-reported outcome questionnaire designed to assess quality of life in patients with leukemia. It includes 27 general items covering physical, social/family, emotional, and functional well-being, along with 17 leukemia-specific items addressing symptoms, treatment concerns, and side effects, for a total of 44 items. Each item is rated on a 5-point Likert scale from 0 ("Not at all") to 4 ("Very much"), with some items reverse-scored for consistency. Scores are summed to create subscale scores and a total score, with higher scores indicating better quality of life. The instrument is commonly used in clinical trials and routine care to monitor patient well-being, evaluate treatment impact, and assess the effects of therapy from the patient's perspective.

Time frame: Baseline and up to 6 months

Change in Functional Assessment of Cancer Therapy (FACT) -Leukemia physical, social, emotional, and functional well-being components

Change in FACT-Leukemia physical, social, emotional, and functional well-being component scores from prior to discontinuation of BTKi to 6 months after discontinuation of BTKi FACT-Leu evaluates patient-reported quality of life across four domains: physical, social/family, emotional, and functional well-being, capturing how a patient's condition evolves over time during or after treatment. Each domain consists of multiple items scored on a 5-point Likert scale ranging from 0 ("not at all") to 4 ("very much"), with domain scores calculated by summing item responses within each domain. A total score may be derived by summing the four core domains (FACT-G) and, when applicable, including leukemia-specific items for the FACT-Leu total score. Higher scores indicate better quality of life.

Time frame: Baseline and up to 6 months

Study on Treatment Outcome Patterns for Patients With CLL After Discontinuation of BTK Inhibitors

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts