Continuing a BTK inhibitor alone versus adding venetoclax for veterans with CLL/SLL
Benefit of Venetoclax Addition ("Benefit VA") in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
This will try adding venetoclax for one year to a BTKi in veterans with CLL or SLL who are already responding, to see if they can stop therapy safely compared with staying on BTKi alone.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 100 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | VA Office of Research and Development Federal |
| Drugs / interventions | ibrutinib, acalabrutinib, zanubrutinib, prednisone |
| Locations | 4 sites (San Francisco, California and 3 other locations) |
| Trial ID | NCT06520098 on ClinicalTrials.gov |
What this trial studies
Veterans with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have been on a stable Bruton Tyrosine Kinase inhibitor (BTKi) for at least six months are randomly assigned to either continue BTKi alone or to add venetoclax for one year. About 100 participants will be enrolled across three VA medical centers, with roughly 50 people per arm. The combination arm receives venetoclax for one year and then stops both drugs, while the BTKi-alone arm continues their current therapy; all participants are closely monitored for disease control, side effects, and quality of life. The trial focuses on patients with low tumor lysis risk and a stable BTKi dose, and uses standard safety measures during venetoclax initiation.
Who should consider this trial
Good fit: Ideal candidates are veterans with CLL or SLL who have been on a stable dose of ibrutinib, acalabrutinib, or zanubrutinib for at least six months, are clinically responding, have ECOG 0–2, detectable disease at screening, and low tumor lysis risk.
Not a fit: Patients who are not responding to BTKi, who have high tumor burden or high tumor lysis risk, or who have unstable comorbidities are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the approach could allow some patients to stop continuous BTKi therapy after a year of added venetoclax, reducing long-term side effects and treatment burden.
How similar studies have performed: Previous trials combining BTKi and venetoclax for one to two years have shown high response rates and have allowed some patients to discontinue therapy, so this study builds on promising prior results.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * CLL or SLL diagnosis * Patients must have been diagnosed with CLL (\> 5000 B-cells per uL of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with \<5000 B-cells per µL of blood but with disease-associated lymphadenopathy by 2018 IWCLL criteria. * Prior treatment * Patients must be currently receiving CLL/SLL directed therapy with a BTKi (i.e., ibrutinib, acalabrutinib, zanubrutinib) for at least six months. * The dose of BTKi must be stable for at least the past three months. * Age 18 years * ECOG performance status 0-2 * Detectable or measurable CLL/SLL in blood or imaging during the screening period. Detectable CLL/SLL in the blood is defined either by elevation in absolute lymphocyte count or by diagnostic flow cytometry from blood demonstrating presence of CLL cells. * Low TLS risk, defined as having all lymph nodes less than 5 cm in diameter (radiographically) and absolute lymphocyte count less than 25 x 109/L in blood, within 30 days of enrollment. * Required initial laboratory values * Absolute Neutrophil Count (ANC) 1,000/mm3 except if due to bone marrow involvement * Platelet Count (untransfused) 30,000/mm3 except if due to bone marrow involvement * Calc. Creatinine Clearance 40 mL/min (by Cockcroft-Gault) * Bilirubin 1.5 x upper limit of normal (ULN) except if due to liver involvement, hemolysis, or Gilbert's disease * AST / ALT 2.5 x upper limit of normal (ULN) except if due to liver involvement * Other * Patients must be able to swallow oral medications and not have the following conditions: disease significantly affecting gastrointestinal absorption, resection of the stomach or small bowel, partial or complete bowel obstruction. * Patients must be able to receive either a xanthine oxidase inhibitor or rasburicase Exclusion Criteria: * Prior treatment * Patients must not have progression of CLL/SLL on BTKi therapy prior to initiation of the study therapy. * Patients must not have received the combination of BTKi + venetoclax previously. * Comorbid conditions or other active diseases * Patients must not have any history of Richter's transformation or prolymphocytic leukemia. * If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable and be on suppressive therapy, if indicated. * Please note: IVIG can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician. * If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load. * Patients with Class III or Class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible. * Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy are eligible for this trial. * Concomitant medications * Patients must not be receiving active systemic anticoagulation with heparin or warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior to registration on the study. * Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not recommended on this study. Patients on strong CYP3A inhibitors must discontinue the drug for 14 days prior to registration on the study or discuss with the study principal investigator. * Chronic concomitant treatment with strong CYP3A4/5 inducers is not recommended. Patients must discontinue the drug 14 days prior to registration on the study or discuss with the study principal investigator. * Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily. * Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics
Where this trial is running
San Francisco, California and 3 other locations
- San Francisco VA Medical Center, San Francisco, CA — San Francisco, California, United States (Recruiting)
- Kansas City VA Medical Center, Kansas City, MO — Kansas City, Missouri, United States (Recruiting)
- Durham VA Medical Center, Durham, NC — Durham, North Carolina, United States (Recruiting)
- VA Puget Sound Health Care System Seattle Division, Seattle, WA — Seattle, Washington, United States (Recruiting)
Study contacts
- Principal investigator: Suman Kambhampati, MD MBBS — Kansas City VA Medical Center, Kansas City, MO
- Study coordinator: Suman Kambhampati, MD MBBS
- Email: suman.kambhampati@va.gov
- Phone: (816) 922-2755
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.