Continuing a BTK inhibitor alone versus adding venetoclax for veterans with CLL/SLL
Official title: Benefit of Venetoclax Addition ("Benefit VA") in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Run by VA Office of Research and Development · NCT06520098 · Data updated 2026-11-12
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 |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Enrollment | 100 (estimated) |
| Sponsor | VA Office of Research and Development Federal |
| Drugs / interventions | ibrutinib, acalabrutinib, zanubrutinib, prednisone |
| Locations | 4 sites (San Francisco, California and 3 other locations) |
| Status | Recruiting |
| Started | October 1, 2025 |
| Main results expected | June 30, 2030 |
| Study ends | December 31, 2030 |
| Registry record updated | October 30, 2026 |
| Trial ID | NCT06520098 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a 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.
✕Probably 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.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
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.
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 gone: 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.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) diagnosis * Patients must have been diagnosed with CLL (\> 5000 B-cells per microliter of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with \<5000 B-cells per microliter 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 Bruton Tyrosine Kinase Inhibitor (BTKi) must be stable for at least the past three months * Eastern Cooperative Oncology Group (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 Tumor Lysis Syndrome (TLS) risk, defined as having all lymph nodes less than 5 centimeters (cm) in diameter (radiographically) and absolute lymphocyte count less than 25 x 109/liter (L) in blood, within 30 days of enrollment * Required initial laboratory values * Absolute Neutrophil Count (ANC) 1,000/ cubic millimeters (mm3) except if due to bone marrow involvement * Platelet Count (untransfused) 30,000/cubic millimeters (mm3) except if due to bone marrow involvement * Calc. Creatinine Clearance 40 milliliters per minute (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 * Aspartate Aminotransferase (AST) / Alanine Aminotransferase (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 Bruton Tyrosine Kinase Inhibitor (BTKi) therapy prior to initiation of the study therapy * Patients must not have received the combination of Bruton Tyrosine Kinase Inhibitor (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: Intravenous immunoglobulin (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 milligrams (mg) prednisone or equivalent corticosteroid daily * Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics
Where it's running
-
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
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
Venetoclax plus Zanubrutinib for CLL/SLL in frontline or previously treated patients
This phase II trial tests if venetoclax plus zanubrutinib can safely and effectively treat adults with chronic lymphocytic leukemia or small lymphocytic lymphoma, including those who are newly diagnosed and those who have had prior therapy.
-
Tafasitamab plus Acalabrutinib and Venetoclax for newly treated CLL/SLL
This phase II study tests a combination of tafasitamab, acalabrutinib, and venetoclax in adults who are newly diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma to see if it is safe and effective.
-
Nemtabrutinib and venetoclax in untreated CLL/SLL
This phase 2 study tests whether combining nemtabrutinib with venetoclax can help people with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.
-
NX-5948 plus other medicines for B-cell cancers
This trial tests NX-5948 in combination with venetoclax, with or without anti-CD20 antibodies, for adults with CLL/SLL or B-cell lymphoma that has returned or worsened or is newly diagnosed but needing treatment.
-
NX-5948 vs Pirtobrutinib in R/R CLL/SLL
This study tests NX-5948 against pirtobrutinib in people with relapsed or refractory CLL/SLL who have previously tried a covalent BTK inhibitor.
-
Rituximab and Tafasitamab with Allogeneic NK Cells for relapsed or refractory B-cell NHL
This trial tests whether giving allogeneic NK cells with Rituximab, Tafasitamab, and IL-2 can help people with relapsed or refractory B-cell non-Hodgkin lymphoma who have tried at least two prior therapies.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.