Recruiting
Phase 2

BTKi vs. Venetoclax

Sponsor:

VA Office of Research and Development

Code:

NCT06520098

Conditions

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Venetoclax

Ibrutinib, Acalabrutinib, Zanubrutinib

Study Details

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 type of pill is called "Bruton Tyrosine Kinase Inhibitor" or BTKi. Another treatment for CLL/SLL is a different pill called venetoclax.

The purpose of this study is to compare continuing the current treatment with BTKi alone, as long as it is working, to another arm of treatment which adds venetoclax to the current treatment (BTKi), for one year. After one year, both pills in this arm of treatment would be stopped and the participants will be closely monitored.

Conditions

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Study ID

NCT06520098

Start date

Oct 1, 2025

Status verified date

Oct, 2025

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Jun 30, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm A : Continue BTKi single agent

Continue BTKi single agent (monotherapy) Standard Intervention

experimental: Arm B : BTKi + Venetoclax for 12 cycles, then discontinue

BTKi + Venetoclax for 12 cycles, then discontinue Experimental Intervention

Interventions

Venetoclax

VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.

Ibrutinib, Acalabrutinib, Zanubrutinib

IMBRUVICA is a kinase inhibitor Acalabrutinib is a selective, irreversible small molecule inhibitor of BTK. Zanubrutinib is BTK inhibitors

Primary outcome measure

  • The primary objective is to evaluate complete response (CR) rate, per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, 2018 [ Time Frame: 24-36 months ]

Central Contacts and Locations

Central contacts

Suman Kambhampati, MD MBBS

(816) 922-2755suman.kambhampati@va.gov

Murali K Nittala, MBBS MS MD

(816) 861-4700murali.nittala@va.gov

Locations

San Francisco VA Medical Center, San Francisco, CA

Recruiting

San Francisco, California, United States, 94121-1563

Contacts

Gerald Hsu, MD

415-221-4810gerald.hsu@va.gov

Kansas City VA Medical Center, Kansas City, MO

Recruiting

Kansas City, Missouri, United States, 64128-2226

Contacts

Murali K Nittala, MBBS MS MD

816-861-4700murali.nittala@va.gov

Principal Investigator:

Suman Kambhampati, MD MBBS

Durham VA Medical Center, Durham, NC

Recruiting

Durham, North Carolina, United States, 27705-3875

Contacts

Daphne Friedman, MD

919-286-0411VHADURCancertrials@va.gov

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Recruiting

Seattle, Washington, United States, 98108-1532

Contacts

Jeannine Barton

206-277-3101Jeannine.Barton@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Oct 14, 2025

Last verified

Oct, 2025

Keywords

  • Leukemia
  • Lymphoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2025-10-14.