Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
Bruton's tyrosine kinase inhibitors (BTKi)
Brief summary
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.
Interventions
OTHERDiscontinuing Bruton tyrosine kinase inhibitors (BTKi) therapy
Discontinuing Bruton tyrosine kinase inhibitors (BTKi) therapy.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 2 years | 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). |
| Overall Survival (OS) | Up to 60 months | Overall Survival (OS) will be defined as the proportion of patients who remain alive after discontinuation of Bruton tyrosine kinase inhibitors (BTKi). |
| Time to initial detection of measurable residual disease (MRD) | Up to 60 months | 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. |
| Overall and complete response rates | 2 years | 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. |
| Rate of resolution of BTKi-related adverse events | 2 years | 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. |
| Incidence of new infections | 1 year | Incidence of new infections will be defined as the percentage of patients who respectively have new infections after discontinuation of BTKi |
| Incidence of second cancers | 5 years | Incidence of second cancers will be defined as the percentage of patients who respectively have second cancers after discontinuation of BTKi. |
| Association between biomarkers and disease outcomes | 5 years | 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). |
| Change in Total Score of Functional Assessment of Cancer Therapy (FACT) -Leukemia | Baseline and up to 6 months | 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. |
| Change in Functional Assessment of Cancer Therapy (FACT) -Leukemia physical, social, emotional, and functional well-being components | Baseline and up to 6 months | 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. |
Countries
United States
Contacts
CONTACTBrice Messenger
CONTACTKatelyn Dempsey
PRINCIPAL_INVESTIGATORDeborah Stephens, DO
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed