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)

NCT06520098 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HEMA-001-23S
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

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

Keywords

Leukemia; Lymphoma

Outcome Measures

Primary Outcomes (1)

• The primary objective is to evaluate complete response (CR) rate, per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, 2018

  The addition of Venetoclax to BTKi for 12 months will improve CR compared to use of BTKi alone in CLL/SLL patients who are already receiving BTKi therapy as treatment.

  24-36 months

Secondary Outcomes (6)

• CLL/SLL patients' experience through patient reported outcome (PRO) measures of fatigue (a key secondary objective)

  24-36 months

• Undetectable minimal residual disease (MRD) in the peripheral blood (PB).

  24-36 months

• Safety and adverse events, measured by Common Terminology Criteria for Adverse Events (CTCAE).

  24-36 months

• Overall response rate (ORR), per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, 2018.

  24 - 36 months

• Measure financial toxicity (FT) in CLL/SLL patients

  24-36 months

Study Arms (2)

Arm A : Continue BTKi single agent

ACTIVE COMPARATOR

Continue BTKi single agent (monotherapy) Standard Intervention

Drug: Ibrutinib, Acalabrutinib, Zanubrutinib

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

EXPERIMENTAL

BTKi + Venetoclax for 12 cycles, then discontinue Experimental Intervention

Drug: Venetoclax; Drug: Ibrutinib, Acalabrutinib, Zanubrutinib

Interventions

Venetoclax DRUG

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.

Also known as: VENCLEXTA

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

Ibrutinib, Acalabrutinib, Zanubrutinib DRUG

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

Also known as: IMBRUVICA, CALQUENCE, BRUKINSA

Arm A : Continue BTKi single agent; Arm B : BTKi + Venetoclax for 12 cycles, then discontinue

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (4)

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121-1563, United States

RECRUITING

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, 64128-2226, United States

RECRUITING

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

RECRUITING

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

Seattle, Washington, 98108-1532, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia; Lymphoma

Interventions

venetoclax; ibrutinib; acalabrutinib; zanubrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Suman Kambhampati, MD MBBS

  Kansas City VA Medical Center, Kansas City, MO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suman Kambhampati, MD MBBS

CONTACT

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

Murali K Nittala, MBBS MS MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: The addition of Venetoclax to BTKi for 12 months in anticipated to improve both the clinical response rates and the quality of life of patients as compared to indefinite use of BTKi monotherapy in CLL/SLL patients

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: July 25, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)