Chronic Lymphocytic LeukemiaPhase 2NCT03128879
Venetoclax With Ibrutinib or Acalabrutinib in Pts. With High-risk CLL
A Phase 2 study testing Ibrutinib, Venetoclax and Acalabrutinib in people with Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This is a single center, open-label, phase II study of venetoclax (ABT-199) added to ibrutinib or acalabrutinib in patients with high-risk CLL who have received at least 12 months of ibrutinib or acalabrutinib monotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Ibrutinib, Venetoclax and Acalabrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jun 2017to 31 May 2027
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a diagnosis of CLL/CLL and have high-risk cytogenetic features or molecular features, defined as: del(17p), mutated TP53, complex metaphase karyotype (defined as 3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis)
- Note: some patients treated with ibrutinib or acalabrutinib may no longer have detectable FISH, karyotypic or molecular abnormalities after 12 months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken either prior to starting ibrutinib or acalabrutinib, provided they did not receive treatment for their CLL between the date of the lab test and starting ibrutinib or acalabrutinib or at some time during their ibrutinib therapy and analyzed at a CLIA-accredited laboratory.
- Patients must have received at least 12 months of ibrutinib or acalabrutinib therapy and have measurable CLL by at least one of the following:
- Absolute monoclonal lymphocyte count > 4000/L; OR
- Measurable lymph nodes with at least one node >1.5 cm in diameter on CT; OR
- Bone marrow with >/= 30% lymphocytes on aspirate differential OR
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- Detectable CLL cells using a standardized flow cytometry assay for minimal residual disease
- Age 18 years or older.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
- Patients must have adequate renal and hepatic function:
- Serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease.
- Serum creatinine clearance of 50ml/min (calculated or measured).
- ALT and AST ≤3.0 x ULN, unless clearly due to disease involvement.
- Adequate bone marrow function:
- Platelet count of greater than 50,000/µl, with no platelet transfusion in prior 2 weeks.
- ANC ≥1000/µl in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by 80% CLL in marrow.
- Hemoglobin ≥8mg/dL.
- INR <1.5.
- Adequate cardiac function, as assessed by:
- Absence of uncontrolled cardiac arrhythmia.
- Echocardiogram demonstrating LVEF ≥35%.
- NYHA functional class ≤2.
- Ability to provide informed consent and adhere to the required follow-up.
- Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence , or sterilized partner) and a barrier method (eg., condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal (defined as absence of menses for ≥1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug.
- Patients or their legally authorized representative must provide written informed consent.
Who cannot join
- Richter transformation.
- Active malignancy requiring systemic therapy, other than CLL, with the exception of: adequately treated in situ carcinoma of the cervix uteri; adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 3 weeks prior to the first dose of the study drug.
- Grade 3 or 4 hemorrhage within the past 3 weeks.
- Uncontrolled active infections (viral, bacterial, and fungal).
- Females who are pregnant or lactating.
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- Known positive serology for human immunodeficiency virus (HIV).
- Active hepatitis B infection (defined as the presence of detectable HBV DNA or HBe antigen). Patients who are HBsAg positive or HBcAb positive are eligible, provided HBV DNA is negative. These patients will have monthly monitoring of HBV DNA for the duration of the study, if clinically indicated. Please note that patients who have received IVIG may have false positive HBcAb results. In such patients, if HBV DNA and HBsAg are negative, serial HBV DNA monitoring is not necessary.
- Active hepatitis C, defined by the detection of hepatitis C RNA in plasma by PCR.
- Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy >20mg prednisone daily or equivalent, within 7 days of starting venetoclax.
- Received other investigational therapeutic agent for CLL/SLL within 21 days of starting venetoclax.
- Concurrent use of warfarin.
- Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax.
- Consuming grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax.
- Prior treatment with venetoclax or other Bcl-2 inhibitor.
- Malabsorption syndrome or other condition that precludes enteral route of administration
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Venetoclax (ABT-199) Consolidation for Patients Currently Receiving Ibrutinib or Acalabrutinib for High-risk CLL
This is a single center, open-label, phase II study of venetoclax (ABT-199) added to ibrutinib or acalabrutinib in patients with high-risk CLL who have received at least 12 months of ibrutinib or acalabrutinib monotherapy.
The study will estimate the therapeutic efficacy of venetoclax consolidation in patients who have detectable CLL after receiving ibrutinib or acalabrutinib for at least 12 months and who have high risk CLL.
Read the detailed description
Primary Objective:
- To estimate the therapeutic efficacy of venetoclax consolidation in patients who have detectable CLL after receiving ibrutinib or acalabrutinib for at least 12 months and who have high risk CLL. High risk is defined as the presence of at least one of: del(17p); TP53 mutation; complex metaphase karyotype; patients who have developed mutations in BTK and/or PLCG2, will be eligible if they have no clinical or laboratory evidence of progressive disease. The primary endpoint will be the rate of MRD-negativity in the bone marrow, using an assay method with at least 0.01% sensitivity after 12 cycles of combination therapy. One cycle is 4 weeks of treatment.
Secondary Objectives:
- Determine CR/CRi rate after 6, 12 18 and 24 cycles of combination therapy, in patients who were not in CR/Cri at study initiation and estimate the time to best response with this combination.
- Determine the cumulative rate of bone marrow minimal residual disease (MRD)-free complete responders by an assay method with at least 0.01% sensitivity and median time to MRD-negativity.
- Determine the safety of combined ibrutinib and venetoclax.
- Determine the progression-free and overall survival.
OUTLINE: This is a dose-escalation study of venetoclax.
Patients receive venetoclax orally (PO) once daily (QD) and ibrutinib PO QD and acalabrutinib PO BID. Treatment repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up every 6-12 months.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Ibrutinib, Venetoclax, Acalabrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
AcalabrutinibDrug
Given BID
| Study group | Role | What they receive |
|---|---|---|
| Treatment (venetoclax, ibrutinib, acalabarutinib) | Experimental | Patients receive venetoclax PO QD and ibrutinib PO QD and acalabrutinib PO BID. Treatment repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unaccepted toxicity. Receives: Drug: Ibrutinib; Drug: Venetoclax; Drug: Acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be the rate of MRD-negativity in the bone marrow, using an assay method with at least 0.01% sensitivity after 12 cycles of combination therapy. One cycle is 4 weeks of treatment.
One cycle is 4 weeks of treatment. (each cycle 28 days)
Measured: through study completion, an average of 1 year
Secondary outcomes (5)
Determine complete remission CR/complete remission with incomplete hematologic recovery CRi rate of combination therapy in patients who were not in CR/Cri at study initiation and estimate the time to best response with this combination.
after 6, 12, 18 and 24 cycles (each cycle 28 days)
Measured: through study completion, an average of 1 year
Determine the cumulative rate of bone marrow minimal residual disease (MRD)-free complete responders by an assay method with at least 0.01% sensitivity and median time to MRD-negativity.
Measured: through study completion, an average of 1 year
Determine the safety of combined ibrutinib and venetoclax.
Safety data will be summarized by category, severity and frequency. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval. The severity of the toxicities will be graded according to the NCI CTCAE v4.0 whenever possible.
Measured: through study completion, an average of 1 year
Determine the progression-free survival
Measured: through study completion, an average of 1 year
Determine the overall survival.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2017
- Study start16 Jun 2017
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alessandra Ferrajoli, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03128879
- Sponsor's protocol ID
- 2016-0785
- Other IDs
- NCI-2018-01182, 2016-0785
- Status last verified
- Aug 2026
- First submitted
- 21 Apr 2017
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Venetoclax (ABT-199) Consolidation for Patients Currently Receiving Ibrutinib or Acalabrutinib for High-risk CLL
- ClinicalTrials.gov ID
- NCT03128879
- Acronym / sponsor ID
- 2016-0785
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 59 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 16 Jun 2017 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 25 Apr 2017 (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.
This is a single center, open-label, phase II study of venetoclax (ABT-199) added to ibrutinib or acalabrutinib in patients with high-risk CLL who have received at least 12 months of ibrutinib or acalabrutinib monotherapy.
The study will estimate the therapeutic efficacy of venetoclax consolidation in patients who have detectable CLL after receiving ibrutinib or acalabrutinib for at least 12 months and who have high risk CLL.
Detailed description
Primary Objective:
- To estimate the therapeutic efficacy of venetoclax consolidation in patients who have detectable CLL after receiving ibrutinib or acalabrutinib for at least 12 months and who have high risk CLL. High risk is defined as the presence of at least one of: del(17p); TP53 mutation; complex metaphase karyotype; patients who have developed mutations in BTK and/or PLCG2, will be eligible if they have no clinical or laboratory evidence of progressive disease. The primary endpoint will be the rate of MRD-negativity in the bone marrow, using an assay method with at least 0.01% sensitivity after 12 cycles of combination therapy. One cycle is 4 weeks of treatment.
Secondary Objectives:
- Determine CR/CRi rate after 6, 12 18 and 24 cycles of combination therapy, in patients who were not in CR/Cri at study initiation and estimate the time to best response with this combination.
- Determine the cumulative rate of bone marrow minimal residual disease (MRD)-free complete responders by an assay method with at least 0.01% sensitivity and median time to MRD-negativity.
- Determine the safety of combined ibrutinib and venetoclax.
- Determine the progression-free and overall survival.
OUTLINE: This is a dose-escalation study of venetoclax.
Patients receive venetoclax orally (PO) once daily (QD) and ibrutinib PO QD and acalabrutinib PO BID. Treatment repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up every 6-12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (venetoclax, ibrutinib, acalabarutinib) | Experimental | Drug: Ibrutinib, Drug: Venetoclax, Drug: AcalabrutinibPatients receive venetoclax PO QD and ibrutinib PO QD and acalabrutinib PO BID. Treatment repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unaccepted toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients must have a diagnosis of CLL/CLL and have high-risk cytogenetic features or molecular features, defined as: del(17p), mutated TP53, complex metaphase karyotype (defined as 3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis)
- Note: some patients treated with ibrutinib or acalabrutinib may no longer have detectable FISH, karyotypic or molecular abnormalities after 12 months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken either prior to starting ibrutinib or acalabrutinib, provided they did not receive treatment for their CLL between the date of the lab test and starting ibrutinib or acalabrutinib or at some time during their ibrutinib therapy and analyzed at a CLIA-accredited laboratory.
- Patients must have received at least 12 months of ibrutinib or acalabrutinib therapy and have measurable CLL by at least one of the following:
- Age 18 years or older.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
Key exclusion criteria (16 listed)
- Richter transformation.
- Active malignancy requiring systemic therapy, other than CLL, with the exception of: adequately treated in situ carcinoma of the cervix uteri; adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 3 weeks prior to the first dose of the study drug.
- Grade 3 or 4 hemorrhage within the past 3 weeks.
- Uncontrolled active infections (viral, bacterial, and fungal).
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 |
|---|---|---|
| IbrutinibAlso: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Given PO | Drug | Treatment (venetoclax, ibrutinib, acalabarutinib) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (venetoclax, ibrutinib, acalabarutinib) |
| AcalabrutinibGiven BID | Drug | Treatment (venetoclax, ibrutinib, acalabarutinib) |
Primary outcome
The primary endpoint will be the rate of MRD-negativity in the bone marrow, using an assay method with at least 0.01% sensitivity after 12 cycles of combination therapy. One cycle is 4 weeks of treatment.
Time frame: through study completion, an average of 1 year
One cycle is 4 weeks of treatment. (each cycle 28 days)
5 secondary outcomes
Determine complete remission CR/complete remission with incomplete hematologic recovery CRi rate of combination therapy in patients who were not in CR/Cri at study initiation and estimate the time to best response with this combination.
Time frame: through study completion, an average of 1 year
Determine the cumulative rate of bone marrow minimal residual disease (MRD)-free complete responders by an assay method with at least 0.01% sensitivity and median time to MRD-negativity.
Time frame: through study completion, an average of 1 year
Determine the safety of combined ibrutinib and venetoclax.
Time frame: through study completion, an average of 1 year
Determine the progression-free survival
Time frame: through study completion, an average of 1 year
Determine the overall survival.
Time frame: through study completion, an average of 1 year
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 10 Aug 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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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. This study is not recruiting at the moment.
Alessandra Ferrajoli, MD principal investigator
M.D. Anderson Cancer Center
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 Ibrutinib, Venetoclax and Acalabrutinib in people with Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center 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 25 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: under way, not looking for participants, as of the sponsor's last update on 10 Aug 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint will be the rate of MRD-negativity in the bone marrow, using an assay method with at least 0.01% sensitivity after 12 cycles of combination therapy. One cycle is 4 weeks of treatment. (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Aug 2026.