Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Conditions
Keywords
ibrutinib, venetoclax, CLL, SLL
Brief summary
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.
Interventions
None listed
Sponsors
European Research Initiative on CLL
Pharmacyclics LLC.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Individuals who meet all of the inclusion criteria will be eligible to participate in the study. 1. Participant is willing and able to give informed consent for participation in this study. 2. Previously enrolled into the CAPTIVATE study. 3. Being treated in a center that has agreed to participate in this follow-up study.
Exclusion criteria
The only exclusion criterion of this study: 1\. Inability or refusal to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type and frequency of second line treatments | Assessed annually after baseline up to 10 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | Assessed annually after baseline up to 10 years | Duration of response (DOR) after ibrutinib + venetoclax. DOR is defined as the time from the onset of response until progression. |
| Complete response rate | Assessed annually after baseline up to 10 years | Complete response rate (CR) for 2nd line treatment assessed per current clinical practice as stated in national and/or international guidelines. |
| Overall response rate | Assessed annually after baseline up to 10 years | 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. |
| Richter transformation rate | Assessed annually after baseline up to 10 years | Richter transformation rate. Richter transformation is defined as the diagnosis of an aggressive lymphoma confirmed by biopsy. |
| Adverse events | Assessed annually after baseline up to 10 years | Adverse event\* rate, type, and grade for first line and second line treatment (only for patients retreated with I+V). |
| Other malignancies | Assessed annually after baseline up to 10 years | Frequency of other malignancies. Other malignancy is defined as the diagnosis of any malignant neoplasm with the exception of CLL and Richter transformation. |
| Progression-free survival for 1st line treatment | 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 (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. |
| Progression-free survival for 2nd line treatment | 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. | 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 to next treatment for 1st line treatment | 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 (TTNT) for 1st line treatment. TTNT is defined as the time from treatment initiation until next treatment for CLL or death. |
| Time to next treatment for 2nd line treatment | 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. | 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 |
| Overall survival | From date of 1st line treatment initiation until date of death from any cause, assessed annually up to 10 years. | Overall survival (OS). OS is defined as the duration from the date of treatment initiation with ibrutinib plus venetoclax to death. |
| Rate of confirmed uMRD for 1st line treatment | Assessed annually after baseline up to 10 years | 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. |
| Rate of confirmed uMRD for 2nd line treatment | Assessed annually after baseline up to 10 years | 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. |
| Molecular characterization of peripheral blood samples at relapse. | Assessed annually after baseline up to 10 years | 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). |
Countries
Italy
Contacts
CONTACTPaolo Ghia, Prof
Outcome results
None listed