Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)

Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) (NCT03986034) is a Phase 2 interventional studying Chronic Lymphocytic Leukemia, sponsored by National Heart, Lung, and Blood Institute (NHLBI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

Background: The drug venetoclax treats chronic lymphocytic leukemia (CLL). Researchers want to find better treatments for CLL. To do that, they need to learn how the drug affects CLL cancer cells and the immune system. Objective: To learn about genetic changes that happen during treatment of CLL with venetoclax. Eligibility: Adults ages 18 and older with relapsed or refractory CLL after at least 1 prior therapy Design: Participants will be screened under a separate protocol. In Phase 1, participants will get venetoclax free of charge through the NIH. Venetoclax is started at a low dose. The dose will be increased every week until participants reach their maximum tolerable dose. This usually take about 5 weeks. Participants will visit the NIH at least once per week. Visits will be about 4 hours. They may have to stay in the hospital to be observed. In Phase 2, participants will continue to get the drug through their local cancer doctor and their health insurance. Patients will also visit the NIH every 6 months, or if their disease progresses. At the NIH participants will have regular health assessments. These will include physical exams and a review of the medicines they are taking. They will talk about how they are feeling. The study included the following tests: Blood draws CT scans: Participants will lie in a machine that takes pictures of the body (maximum 3 per year) Bone marrow biopsies: A small amount of marrow will be taken out of the participant s hip bone with a needle. Optional lymph node biopsies: A small piece of the participant s tissue will be taken out with a needle. The study will last at least 2 years.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Chronic Lymphocytic Leukemia and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 75 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Chronic Lymphocytic Leukemia subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

-Who May Qualify: 1. Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI Working Group. 2. Active disease as defined by at least one of the following (iwCLL consensus criteria): - Weight loss \>=10% within the previous 6 months - Extreme fatigue - Fevers of greater than 100.5 degrees F for \>=2 weeks without evidence of infection - Night sweats for more than one month without evidence of infection - Evidence of progressive marrow failure as manifested by the development of, or worsening of - Anemia and/or thrombocytopenia - Massive or progressive splenomegaly - Massive nodes or clusters or progressive lymphadenopathy - Progressive lymphocytosis with an increase of \>50% over a 2-month period, or an anticipated doubling time of less than 6 months 3. Must have designated hematologist/oncologist will assume care and provide venetoclax after the ramp-up phase is complete 4. Must have G6PD testing performed to determine whether rasburicase can be given 5. Must have HLA-testing performed to determine whether allopurinol hypersensitivity exists 6. Age \>=18 years 7. ECOG 0-2 8. Agreement to use acceptable methods of contraception for the duration of venetoclax treatment if sexually active and able to bear or beget children 9. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty 10. Able to comprehend the investigational nature of the protocol and provide willing to sign a consent form Who Should NOT Join This Trial: 1. Female patients who are currently pregnant or nursing 2. Any uncontrolled active systemic infection 3. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator s opinion, could compromise the subject s safety or put the study outcomes at undue risk 4. Known additional malignancy that is progressing or requires active treatment. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

-INCLUSION CRITERIA: 1. Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI Working Group. 2. Active disease as defined by at least one of the following (iwCLL consensus criteria): * Weight loss \>=10% within the previous 6 months * Extreme fatigue * Fevers of greater than 100.5 degrees F for \>=2 weeks without evidence of infection * Night sweats for more than one month without evidence of infection * Evidence of progressive marrow failure as manifested by the development of, or worsening of * Anemia and/or thrombocytopenia * Massive or progressive splenomegaly * Massive nodes or clusters or progressive lymphadenopathy * Progressive lymphocytosis with an increase of \>50% over a 2-month period, or an anticipated doubling time of less than 6 months 3. Must have designated hematologist/oncologist will assume care and provide venetoclax after the ramp-up phase is complete 4. Must have G6PD testing performed to determine whether rasburicase can be given 5. Must have HLA-testing performed to determine whether allopurinol hypersensitivity exists 6. Age \>=18 years 7. ECOG 0-2 8. Agreement to use acceptable methods of contraception for the duration of venetoclax treatment if sexually active and able to bear or beget children 9. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty 10. Able to comprehend the investigational nature of the protocol and provide informed consent EXCLUSION CRITERIA: 1. Female patients who are currently pregnant or nursing 2. Any uncontrolled active systemic infection 3. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator s opinion, could compromise the subject s safety or put the study outcomes at undue risk 4. Known additional malignancy that is progressing or requires active treatment. --Note: Exceptions include basal cell carcinoma of skin, squamous cell carcinoma of skin, and in situ cervical cancer that has undergone potentially curative therapy. Further exceptions include other cancers from which the subject has been diseasefree for \> 2 years, cancers which will not limit survival to \< 2 years or cancers in remission receiving endocrine therapy. 5. Richter s Transformation 6. Any prior therapy with BCL-2 inhibitors 7. Concomitant use of strong CYP3A4 inhibitors 8. Disease significantly affecting gastrointestinal function or absorption 9. Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia 10. Concomitant systemic cancer directed therapy (e.g. immunotherapy, chemotherapy, radiotherapy) 11. Absolute neutrophil count (ANC) \<1000/microL, platelets (Plt) \<30,000/ microL 12. Serum bilirubin \>3 times upper limit of normal (ULN) 13. Severe psychiatric illness/social situations or cognitive impairment that would limit the patient s ability to tolerate and/or comply with study requirements * If the PI assesses the decreased ANC and/or Plt to be related to CLL involvement, patients may still be enrolled in the study, as cytopenias as expected to improve with treatment of CLL. Patients may receive supportive measures (e.g. transfusions, IVIG, growth factor support, etc.) to avoid severe cytopenias prior to and during therapy with venetoclax.

Treatments Being Tested

DRUG

During Venetoclax

Patients with CLL/SLL will enroll on the study. Subjects will be treated at the NIH Clinical Center for the duration of the ramp-up phase of venetoclax. After the ramp-up phase is complete, subjects will be transitioned to the care of their local hematologist/oncologist and receive venetoclax monotherapy or in combination with other agent(s) at the discretion of the treating oncologist. Subjects will have the option to follow-up at the NIH every 6 months (from initiation of venetoclax) and at (suspected) progression.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03986034), the sponsor (National Heart, Lung, and Blood Institute (NHLBI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03986034 clinical trial studying?

Who can participate in NCT03986034?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03986034?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03986034. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03986034. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.