Status:
RECRUITING
A Randomized Phase II Study Of Bruton Tyrosine Kinase Inhibitor With Or Without Venetoclax In Veterans With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Lead Sponsor:
VA Office of Research and Development
Conditions:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Eligibility:
All Genders
18-80 years
Phase:
PHASE2
Brief Summary
People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that are taken by mouth. This t...
Detailed Description
People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that are taken by mouth. This t...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
October 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2030
Estimated Enrollment :
100 Patients enrolled
Trial Details
Trial ID
NCT06520098
Start Date
October 1 2025
End Date
December 31 2030
Last Update
October 14 2025
Active Locations (4)
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1
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, United States, 94121-1563
2
Kansas City VA Medical Center, Kansas City, MO
Kansas City, Missouri, United States, 64128-2226
3
Durham VA Medical Center, Durham, NC
Durham, North Carolina, United States, 27705-3875
4
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, United States, 98108-1532