Chronic Lymphocytic LeukemiaPhase 2NCT03986034
Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
A Phase 2 study testing During Venetoclax in people with Chronic Lymphocytic Leukemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- During Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jun 2019to 17 Nov 2026
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Female patients who are currently pregnant or nursing
- Any uncontrolled active systemic infection
- 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
- 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.
- Richter s Transformation
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- Any prior therapy with BCL-2 inhibitors
- Concomitant use of strong CYP3A4 inhibitors
- Disease significantly affecting gastrointestinal function or absorption
- Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
- Concomitant systemic cancer directed therapy (e.g. immunotherapy, chemotherapy, radiotherapy)
- Absolute neutrophil count (ANC) <1000/microL, platelets (Plt) <30,000/ microL
- Serum bilirubin >3 times upper limit of normal (ULN)
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)
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.
Read more
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.
Read the detailed description
This study aims to study the clonal dynamics and kinetics of response during the ramp-up phase of venetoclax in chronic lymphocytic leukemia (CLL).
Key Eligibility Criteria:
- Diagnosis of CLL/SLL (treatment naive or relapsed/refractory)
- Must have designated hematologist/oncologist who has agreed to assume care and continue venetoclax after the ramp-up phase is complete
- Age >=18 years
- ECOG 0-2
Design:
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.
Study Objectives:
Primary Objective:
-Determine the proportion of subjects with clonal shift during the ramp-up phase of venetoclax
Secondary Objective:
-Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow
Exploratory Objectives:
- Assess relationship between clonal shifts and minimal residual disease (MRD) status, progression free survival (PFS) and overall survival (OS)
- Assess immunologic changes in the peripheral blood and bone marrow during venetoclax treatment
- Assess circulating-tumor DNA in response to treatment during venetoclax treatment
- Compare the proportion of subjects with early clonal shift between patients receiving only venetoclax and patients receiving venetoclax and BTKi overlap during the ramp-up
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- During Venetoclax
- Keywords
- ramp-up, Rituximab, Tumor, Treatment, Cancer
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
During VenetoclaxDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Relapsed/Refractory CLL pts | Experimental | Ages 18 and older Receives: Drug: During Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the rate of clonal shift during the ramp-up phase of venetoclax
The planned analyses will include descriptive statistics on the proportions of clonal shift probability during the venetoclax ramp-up phase. The clonal shift probabilities will be estimated using the sample proportions and their inferences including confidence intervals and hypotheses testing will be evaluated
Measured: 5 weeks.
Secondary outcomes (1)
a. Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow
Measured: 5 weeks (Primary Endpoint). F/u every 6 months thereafter until disease progression.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start26 Jun 2019
- Primary completion17 Nov 2026 (estimated)
- Study completion17 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christine E Gruessner, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03986034
- Sponsor's protocol ID
- 190111
- Other IDs
- 19-H-0111
- Status last verified
- 18 Sep 2026
- First submitted
- 13 Jun 2019
- Last updated
- 24 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The study team is still deciding.
Publications
Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):311-22. doi: 10.1056/NEJMoa1513257. Epub 2015 Dec 6.
PubMed 26639348Herling CD, Abedpour N, Weiss J, Schmitt A, Jachimowicz RD, Merkel O, Cartolano M, Oberbeck S, Mayer P, Berg V, Thomalla D, Kutsch N, Stiefelhagen M, Cramer P, Wendtner CM, Persigehl T, Saleh A, Altmuller J, Nurnberg P, Pallasch C, Achter V, Lang U, Eichhorst B, Castiglione R, Schafer SC, Buttner R, Kreuzer KA, Reinhardt HC, Hallek M, Frenzel LP, Peifer M. Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia. Nat Commun. 2018 Feb 20;9(1):727. doi: 10.1038/s41467-018-03170-7.
PubMed 29463802Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, Puvvada SD, Wendtner CM, Roberts AW, Jurczak W, Mulligan SP, Bottcher S, Mobasher M, Zhu M, Desai M, Chyla B, Verdugo M, Enschede SH, Cerri E, Humerickhouse R, Gordon G, Hallek M, Wierda WG. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016 Jun;17(6):768-778. doi: 10.1016/S1470-2045(16)30019-5. Epub 2016 May 10.
PubMed 27178240
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT03986034
- Acronym / sponsor ID
- 190111
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- ramp-up, Rituximab, Tumor, Treatment, Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 26 Jun 2019 (actual)
- Primary completion
- 17 Nov 2026 (estimated)
- Study completion
- 17 Nov 2026 (estimated)
- First posted
- 14 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study aims to study the clonal dynamics and kinetics of response during the ramp-up phase of venetoclax in chronic lymphocytic leukemia (CLL).
Key Eligibility Criteria:
- Diagnosis of CLL/SLL (treatment naive or relapsed/refractory)
- Must have designated hematologist/oncologist who has agreed to assume care and continue venetoclax after the ramp-up phase is complete
- Age >=18 years
- ECOG 0-2
Design:
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.
Study Objectives:
Primary Objective:
-Determine the proportion of subjects with clonal shift during the ramp-up phase of venetoclax
Secondary Objective:
-Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow
Exploratory Objectives:
- Assess relationship between clonal shifts and minimal residual disease (MRD) status, progression free survival (PFS) and overall survival (OS)
- Assess immunologic changes in the peripheral blood and bone marrow during venetoclax treatment
- Assess circulating-tumor DNA in response to treatment during venetoclax treatment
- Compare the proportion of subjects with early clonal shift between patients receiving only venetoclax and patients receiving venetoclax and BTKi overlap during the ramp-up
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Relapsed/Refractory CLL pts | Experimental | Drug: During VenetoclaxAges 18 and older |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Female patients who are currently pregnant or nursing
- Any uncontrolled active systemic infection
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| During VenetoclaxPatients 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. | Drug | Relapsed/Refractory CLL pts |
Primary outcome
Determine the rate of clonal shift during the ramp-up phase of venetoclax
Time frame: 5 weeks.
The planned analyses will include descriptive statistics on the proportions of clonal shift probability during the venetoclax ramp-up phase. The clonal shift probabilities will be estimated using the sample proportions and their inferences including confidence intervals and hypotheses testing will be evaluated
1 secondary outcome
a. Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow
Time frame: 5 weeks (Primary Endpoint). F/u every 6 months thereafter until disease progression.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Background: PubMed 26639348Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):311-22. doi: 10.1056/NEJMoa1513257. Epub 2015 Dec 6.
- Background: PubMed 29463802Herling CD, Abedpour N, Weiss J, Schmitt A, Jachimowicz RD, Merkel O, Cartolano M, Oberbeck S, Mayer P, Berg V, Thomalla D, Kutsch N, Stiefelhagen M, Cramer P, Wendtner CM, Persigehl T, Saleh A, Altmuller J, Nurnberg P, Pallasch C, Achter V, Lang U, Eichhorst B, Castiglione R, Schafer SC, Buttner R, Kreuzer KA, Reinhardt HC, Hallek M, Frenzel LP, Peifer M. Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia. Nat Commun. 2018 Feb 20;9(1):727. doi: 10.1038/s41467-018-03170-7.
- Background: PubMed 27178240Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, Puvvada SD, Wendtner CM, Roberts AW, Jurczak W, Mulligan SP, Bottcher S, Mobasher M, Zhu M, Desai M, Chyla B, Verdugo M, Enschede SH, Cerri E, Humerickhouse R, Gordon G, Hallek M, Wierda WG. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016 Jun;17(6):768-778. doi: 10.1016/S1470-2045(16)30019-5. Epub 2016 May 10.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. The study team is still deciding.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christine E Gruessner, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing During Venetoclax in people with Chronic Lymphocytic Leukemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site 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 0 inclusion and 15 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 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Ingrid C Frey ((301) 402-0797, ingrid.frey@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the rate of clonal shift during the ramp-up phase of venetoclax (time frame: 5 weeks.). 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 NCT03986034, which also lists 3 linked publications.
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 24 Sep 2026.