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Chronic Lymphocytic LeukemiaPhase 2Benefit VANCT06520098

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)

A Phase 2 study testing Venetoclax and Ibrutinib, Acalabrutinib, Zanubrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by VA Office of Research and Development at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Venetoclax and Ibrutinib, Acalabrutinib, Zanubrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
4 sitesUnited States
Study dates
1 Oct 2025to 31 Dec 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Suman Kambhampati, MD MBBS contact

(816) 922-2755

suman.kambhampati@va.gov

Murali K Nittala, MBBS MS MD contact

(816) 861-4700 ext. 57840

murali.nittala@va.gov

United States4 sites, 4 recruiting

  • Durham VA Medical Center, Durham, NC

    Durham, North Carolina, 27705-3875

    Daphne Friedman, MD, 919-286-0411, VHADURCancertrials@va.gov

    Recruiting

  • Kansas City VA Medical Center, Kansas City, MO

    Kansas City, Missouri, 64128-2226

    Murali K Nittala, MBBS MS MD, (816) 861-4700 ext. 57840, murali.nittala@va.gov

    Suman Kambhampati, MD MBBS

    Recruiting

  • San Francisco VA Medical Center, San Francisco, CA

    San Francisco, California, 94121-1563

    Gerald Hsu, MD, 415-221-4810 ext. 24343, gerald.hsu@va.gov

    Recruiting

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

    Seattle, Washington, 98108-1532

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

    Recruiting

Other trials in United States

About this study

Official title: Benefit of Venetoclax Addition ("Benefit VA") in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

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.

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

People with CLL/SLL who are currently taking BTKi as their treatment must continue to take the medicine for the rest of their lives (unless it is no longer working or causing difficult side effects).

New studies tested the combination of BTKi and venetoclax for one to two years, and showed that it was a very effective treatment, and allowed patients to stop therapy.

The investigators don't know if adding venetoclax in patients who have already taken BTKi therapy for at least six months and who are responding to it will help control the CLL/SLL better and if it will allow them to stop treatment safely. Also, the investigators don't know how the side effects and effectiveness of the combination will be in Veterans. The investigators also don't know how a patient's quality of life will be affected if they continue BTKi by itself or if they take the combination and then are able to stop treatment.

If participants meet the eligibility criteria, they will be randomly assigned a study treatment. This study has 2 main study groups:

ARM A (BTKI ALONE): There will be about 50 people in this group.

ARM B (BTKI PLUS VENETOCLAX): There will be about 50 people in this group.

The participants will not be charged for any treatments or procedures that are part of this study. If participants usually pay co-payments for VA care and medications, they will still pay these co-payments for VA care and medications that are not part of this study.

Being tested
Venetoclax, Ibrutinib, Acalabrutinib, Zanubrutinib
Keywords
Leukemia, Lymphoma
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenetoclaxDrug

    Also called VENCLEXTA

    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, ZanubrutinibDrug

    Also called IMBRUVICA, CALQUENCE, BRUKINSA

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

Study groups in NCT06520098
Study groupRoleWhat they receive
Arm A : Continue BTKi single agentActive comparatorContinue BTKi single agent (monotherapy) Standard Intervention
Receives: Drug: Ibrutinib, Acalabrutinib, Zanubrutinib
Arm B : BTKi + Venetoclax for 12 cycles, then discontinueExperimentalBTKi + Venetoclax for 12 cycles, then discontinue Experimental Intervention
Receives: Drug: Venetoclax; Drug: Ibrutinib, Acalabrutinib, Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24-36 months

Secondary outcomes (6)

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

    The addition of Venetoclax to BTKi for 12 months is anticipated to improve cancer-related fatigue as compared to use of BTKi alone in CLL/SLL patients. FACIT-Fatigue PRO instrument will be used.

    Measured: 24-36 months

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

    Use residual disease (MRD) assays in the peripheral blood (PB).

    Measured: 24-36 months

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

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

    Measured: 24-36 months

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

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

    Measured: 24 - 36 months

  5. Measure financial toxicity (FT) in CLL/SLL patients

    The addition of Venetoclax to BTKi for 12 months is anticipated to improve cancer-related fatigue as compared to use of BTKi alone in CLL/SLL patients. FACT-COST PRO instrument will be used. The score ranges between 0 and 44, and a higher score implies better financial well-being.

    Measured: 24-36 months

  6. CLL/SLL patients' experience through patient reported outcome (PRO) QoL

    The addition of Venetoclax to BTKi for 12 months is anticipated to improve of cancer-related fatigue as compared to use of BTKi alone in CLL/SLL patients. Aggregate scores from PRO instruments (QLQ-C30, QLQ-CLL17) will be used. These multi-item scales range in score from 0 to 100. A high score on these scales represents a high level of symptomatology or problems.

    Measured: 24-36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2024
  2. Study start1 Oct 2025
  3. Primary completion30 Jun 2030 (estimated)
  4. Study completion31 Dec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06520098
Sponsor's protocol ID
HEMA-001-23S
Other IDs
1I01CX002685-01A1
Acronym
Benefit VA
Status last verified
Oct 2026
First submitted
12 Feb 2024
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax and Ibrutinib, Acalabrutinib, Zanubrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by VA Office of Research and Development at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Suman Kambhampati, MD MBBS ((816) 922-2755, suman.kambhampati@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06520098.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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