Study on Treatment Outcome Patterns for Patients With CLL After Discontinuation of BTK Inhibitors (STOP-CLL-DCT)

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 Overview

• Status: Not yet recruiting
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Other: Discontinuing Bruton tyrosine kinase inhibitors (BTKi) therapy

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Brice Messenger; Phone Number: 919-984-0000; Email: brice_messenger@med.unc.edu
• Study Contact Backup: Name: Katelyn Dempsey; Phone Number: 919-984-0000; Email: katelyn_dempsey@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Principal Investigator: Deborah Stephens, DO
      • Contact: Brice Messenger; Phone Number: 919-984-0000; Email: brice_messenger@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have been receiving covalent Bruton tyrosine kinase inhibitors for at least 2 years and have achieved a clinical remission.	Other: Discontinuing Bruton tyrosine kinase inhibitors (BTKi) therapy; Discontinuing Bruton tyrosine kinase inhibitors (BTKi) therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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.	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.	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.	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	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.	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).	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.	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.	Baseline and up to 6 months

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Deborah Stephens, DO, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): June 1, 2032

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Bruton's tyrosine kinase inhibitors (BTKi)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Therapeutics
• Other Study ID Numbers: LCCC2522-DCT

Drug and device information, study documents

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