This study is focused on tracking the long-term health of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) treated with a combination of two drugs, ibrutinib and venetoclax, as part of the original CAPTIVATE clinical trial. Purpose and Goals While new treatments have significantly improved survival for patients with CLL, the disease remains incurable and often requires multiple rounds of treatment over a person's life. The primary goal of this study is to understand what happens to patients after they have completed their initial (frontline) treatment with a combination of two drugs, ibrutinib and venetoclax, as part of the original CAPTIVATE clinical trial. Researchers specifically want to: * Identify the types and frequency of "second-line" treatments patients receive if their disease returns. * Assess the long-term safety and effectiveness of the initial ibrutinib and venetoclax treatment. * Study how the disease might become resistant to these treatments over time. Who Can Participate? The study is specifically for individuals who were previously enrolled in the original CAPTIVATE study. Only patients at participating medical centers who provide their informed consent can join. Study Methods and Procedures This is an observational study, meaning researchers will monitor patients' health during their routine medical care rather than testing a new, experimental treatment. Key aspects of the study include: * Long-Term Monitoring: Patients will be followed for up to 10 years. * Data Collection: Researchers will collect information on disease status, treatment history, new health issues (comorbidities), and survival. * Optional Testing: With additional consent, patients may provide blood samples every six months to check for "measurable residual disease" (MRD)-very small amounts of cancer cells that remain after treatment. * Genetic Analysis: If a patient's CLL progresses, researchers may analyze blood samples to look for specific genetic mutations that might explain why the treatment stopped working. Participation is entirely voluntary, and patients can choose to withdraw from the study or opt out of specific tests (like blood sampling) at any time without affecting their standard medical care.
Study Type
OBSERVATIONAL
Enrollment
323
IRCCS Ospedale San Raffaele
Milan, Italy
RECRUITINGType and frequency of second line treatments
Type and frequency of second line treatments (including re-treatment with ibrutinib or ibrutinib + venetoclax) of patients with CLL treated with the combination of frontline ibrutinib plus venetoclax in the CAPTIVATE study.
Time frame: Assessed annually after baseline up to 10 years
Duration of response
Duration of response (DOR) after ibrutinib + venetoclax. DOR is defined as the time from the onset of response until progression.
Time frame: Assessed annually after baseline up to 10 years
Complete response rate
Complete response rate (CR) for 2nd line treatment assessed per current clinical practice as stated in national and/or international guidelines.
Time frame: Assessed annually after baseline up to 10 years
Overall response rate
Overall response rate (ORR) for 2nd line treatment. ORR is defined as the percentage of participants achieving a best overall response of CR, CR with incomplete blood count recovery (CRi), nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PRL). CR, CRi, nPR, PR, and PRL are defined as per 2018 IWCLL criteria.
Time frame: Assessed annually after baseline up to 10 years
Richter transformation rate
Richter transformation rate. Richter transformation is defined as the diagnosis of an aggressive lymphoma confirmed by biopsy.
Time frame: Assessed annually after baseline up to 10 years
Adverse events
Adverse event\* rate, type, and grade for first line and second line treatment (only for patients retreated with I+V).
Time frame: Assessed annually after baseline up to 10 years
Other malignancies
Frequency of other malignancies. Other malignancy is defined as the diagnosis of any malignant neoplasm with the exception of CLL and Richter transformation.
Time frame: Assessed annually after baseline up to 10 years
Progression-free survival for 1st line treatment
Progression-free survival (PFS) for 1st line treatment. PFS is defined as the time from 1st line treatment initiation until CLL progression or death. CLL progression is defined as per 2018 IWCLL criteria.
Time frame: From date of 1st line treatment initiation until date of documented disease progression or death from any cause, whichever comes first, assessed annually up to 10 years.
Progression-free survival for 2nd line treatment
Progression-free survival (PFS) for 2nd line treatment. PFS is defined as the time from 2nd line treatment initiation until CLL progression or death. CLL progression is defined as per 2018 IWCLL criteria.
Time frame: From date of 2nd line treatment initiation until date of documented disease progression or death from any cause, whichever comes first, assessed annually up to 10 years.
Time to next treatment for 1st line treatment
Time to next treatment (TTNT) for 1st line treatment. TTNT is defined as the time from treatment initiation until next treatment for CLL or death.
Time frame: From date of 1st line treatment initiation until date of next treatment for CLL or death from any cause, whichever comes first, assessed annually up to 10 years.
Time to next treatment for 2nd line treatment
Time to next treatment (TTNT) for 2nd line treatment. TTNT is defined as the time from treatment initiation until next treatment for CLL or death. \*Assessed annually after baseline up to 10 years
Time frame: From date of 2nd line treatment initiation until date of next treatment for CLL or death from any cause, whichever comes first, assessed annually up to 10 years.
Overall survival
Overall survival (OS). OS is defined as the duration from the date of treatment initiation with ibrutinib plus venetoclax to death.
Time frame: From date of 1st line treatment initiation until date of death from any cause, assessed annually up to 10 years.
Rate of confirmed uMRD for 1st line treatment
Rate of confirmed uMRD for 1st line treatment assessed every 6 months in the fixed-duration cohort and the placebo arm of the MRD cohort. uMRD is defined as \< 1 CLL cell per 10,000 leukocytes, serially over ≥ 2 assessments ≥ 3 months apart, in PB assessed by 8- color flow cytometry.
Time frame: Assessed annually after baseline up to 10 years
Rate of confirmed uMRD for 2nd line treatment
Rate of confirmed uMRD for 2nd line treatment assessed every 6 months in patients retreated with I+V. uMRD is defined as \< 1 CLL cell per 10,000 leukocytes, serially over ≥ 2 assessments ≥ 3 months apart, in PB assessed by 8-color flow cytometry.
Time frame: Assessed annually after baseline up to 10 years
Molecular characterization of peripheral blood samples at relapse.
Molecular characterization of peripheral blood samples at relapse. Assessment for mutations in BTK, PLCG2, and BCL2 genes in patients who relapsed after I+V (given as first line or/and retreatment).
Time frame: Assessed annually after baseline up to 10 years
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