AzTrials
AzTrials

Chronic Lymphocytic LeukemiaPhase 2NCT02756897

Venetoclax and Ibrutinib in Treating Patients With Chronic or Small Lymphocytic Leukemia

A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Venetoclax in people with Chronic Lymphocytic Leukemia and Recurrent Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well venetoclax and ibrutinib work in treating patients with chronic or small lymphocytic leukemia. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
234 participants
Where
1 siteUnited States
Study dates
7 Jul 2016to 1 Jul 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 with a diagnosis of CLL/SLL:
  • Cohort 1: Refractory to and/or relapsed after at least one prior therapy will be eligible
  • Cohort 2: Untreated patients with high-risk features (del(17p), or mutated TP53, or del(11q), or unmutated IGHV, or >= 65 years of age) are eligible (cohort 2) provided they have active disease requiring treatment as defined by the International Working Group for CLL (IWCLL)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN for patients with Gilbert's disease (in patients [pts] with elevated total bilirubin due to increased indirect bilirubin, pts with direct bilirubin =< 1.5 x ULN are eligible)
  • Creatinine clearance > 50 mL/min (calculated according to institutional standards or using Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD], or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
Show all 11Show fewer
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN, unless clearly due to disease involvement
  • Platelet count of greater than 20,000/mul, with no platelet transfusion in 2 weeks prior to registration; this criteria is waived if the thrombocytopenia is due to bone marrow involvement with the disease
  • Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug; women of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy; men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
  • Free of prior malignancies for 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast, who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 2 years prior to study enrolment; if patients have another malignancy that was treated within the last 2 years, such patients may be enrolled if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center, and after consultation with the principal investigator
  • Patients or their legally authorized representative must provide written informed consent

Who cannot join

  • Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, investigational therapy within 3 weeks prior to the first dose of the study drugs
  • Uncontrolled active systemic infection (viral, bacterial, and fungal)
  • Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs
  • Active hepatitis B infection (defined as the presence of detectable hepatitis B virus [HBV] deoxyribonucleic acid [DNA], hepatitis B e [HBe] antigen or hepatitis B surface [HBs] antigen); subjects with serologic evidence of prior vaccination (hepatitis B surface antigen [HBsAg] negative, anti-HBs antibody positive, anti-hepatitis B core [HBc] antibody negative) are eligible; patients who are HBsAg negative/hepatitis B surface antibody (HBsAb) positive but hepatitis B core antibody (HBcAb) positive are eligible, provided HBV DNA is negative
  • Active hepatitis C, defined by the detectable hepatitis C ribonucleic acid (RNA) in plasma by polymerase chain reaction (PCR)
  • Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent
Show all 14Show fewer
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 2 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Patient is pregnant or breast-feeding
  • Concurrent use of warfarin
  • Received strong (CYP3A) inhibitors or strong CYP3A inducers within 7 days of starting study drugs
  • Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting study drugs
  • Prior treatment with venetoclax or ibrutinib
  • Malabsorption syndrome or other condition that precludes enteral route of administration
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study of Venetoclax and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL)

This phase II trial studies how well venetoclax and ibrutinib work in treating patients with chronic or small lymphocytic leukemia. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax and ibrutinib may help control chronic or small lymphocytic leukemia.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Estimate therapeutic activity (best response [complete response (CR)/complete response with incomplete recovery (CRi)]) of combined ibrutinib and venetoclax in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL).

SECONDARY OBJECTIVES:

  1. To determine the safety of this combination strategy. II. To estimate the time to best response with this combination. III. To determine the progression-free survival (PFS) and overall survival (OS).

IV. To test pharmacodynamic endpoints and molecular interactions between these two drugs.

  1. To assess the therapeutic activity (best response [CR/CRi]) in subgroups of patients defined by immunoglobulin heavy chain variable (IGHV) mutation or fluorescence in situ hybridization (FISH) subtype.

EXPLORATORY OBJECTIVE:

  1. To study immunological and molecular changes in the peripheral blood and the bone marrow in response to ibrutinib and venetoclax.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning on day 1 of cycle 4, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients with residual disease or who are positive for minimal residual disease (MRD) after cycle 27 may continue treatment with ibrutinib.

After completion of study treatment, patients are followed up every 3-6 months.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Venetoclax
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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT02756897
Study groupRoleWhat they receive
Treatment (ibrutinib, venetoclax)ExperimentalPatients receive ibrutinib PO QD on days 1-28. Beginning on day 1 of cycle 4, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients with residual disease or who are positive for MRD after cycle 27 may continue treatment with ibrutinib.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Venetoclax

What is being measured

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

  1. Best response (complete response /complete response with incomplete recovery) of combined ibrutinib and venetoclax

    For each cohort, the best response (complete response /complete response with incomplete recovery) rate will be estimated along with the exact 95% confidence interval.

    Measured: Up to 2 months after treatment

Secondary outcomes (5)

  1. Incidence of toxicities

    Will be defined as prolonged neutropenia or thrombocytopenia lasting > 42 days; febrile neutropenia; hospitalization due to infection; early death; major bleeding due to thrombocytopenia. Will be monitored in each disease cohort separately using the Bayesian method of Thall, Simon and Estey. Safety data will be summarized using descriptive statistics.

    Measured: Up to 6 weeks of treatment

  2. Time to response with combination of ibrutinib and venetoclax

    Estimated using the Kaplan-Meier method in each cohort.

    Measured: Up to 8 years

  3. Overall survival

    Estimated using the Kaplan-Meier method in each cohort.

    Measured: Up to 8 years

  4. Progression-free survival

    Estimated using the Kaplan-Meier method in each cohort.

    Measured: Up to 8 years

  5. Complete response/complete response with incomplete recovery rate in each subgroups of patients

    Will be defined by IGHV mutation or fluorescence in situ hybridization (FISH) subtype. Will be estimated along with the exact 95% confidence interval.

    Measured: Up to 8 years

Timeline

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

  1. First posted29 Apr 2016 (estimated)
  2. Study start7 Jul 2016
  3. Primary completion1 Jul 2027 (estimated)
  4. Study completion1 Jul 2027 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
234 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02756897
Sponsor's protocol ID
2015-0860
Other IDs
NCI-2016-00797, 2015-0860
Status last verified
Aug 2026
First submitted
26 Apr 2016
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Swaminathan M, Ferrajoli A, Thompson PA, Burger J, Borthakur G, Takahashi K, Estrov Z, Bharathi V, Bataller A, Kadia TM, Pemmaraju N, Daver N, Jabbour E, Bose P, Kanagal-Shamanna R, Patel KP, Wang SA, Garg N, Hwang H, Wang X, Qiao W, Xu X, Cruz N, Ayala A, Pierce S, Plunkett W, Sampath D, Kantarjian HM, Keating MJ, Gandhi V, Wierda WG, Jain N. Ibrutinib with Venetoclax in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: A Phase II Study. Blood Cancer Discov. 2026 May 5;7(3):431-440. doi: 10.1158/2643-3230.BCD-25-0345.

    PubMed 41678768

  • Jain N, Keating M, Thompson P, Ferrajoli A, Burger JA, Borthakur G, Takahashi K, Estrov Z, Sasaki K, Fowler N, Kadia T, Konopleva M, Alvarado Y, Yilmaz M, DiNardo C, Bose P, Ohanian M, Pemmaraju N, Jabbour E, Kanagal-Shamanna R, Patel K, Wang W, Jorgensen J, Wang SA, Garg N, Wang X, Wei C, Cruz N, Ayala A, Plunkett W, Kantarjian H, Gandhi V, Wierda WG. Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia: A Nonrandomized Phase 2 Trial. JAMA Oncol. 2021 Aug 1;7(8):1213-1219. doi: 10.1001/jamaoncol.2021.1649.

    PubMed 34110383

  • Jain N, Keating M, Thompson P, Ferrajoli A, Burger J, Borthakur G, Takahashi K, Estrov Z, Fowler N, Kadia T, Konopleva M, Alvarado Y, Yilmaz M, DiNardo C, Bose P, Ohanian M, Pemmaraju N, Jabbour E, Sasaki K, Kanagal-Shamanna R, Patel K, Jorgensen J, Garg N, Wang X, Sondermann K, Cruz N, Wei C, Ayala A, Plunkett W, Kantarjian H, Gandhi V, Wierda W. Ibrutinib and Venetoclax for First-Line Treatment of CLL. N Engl J Med. 2019 May 30;380(22):2095-2103. doi: 10.1056/NEJMoa1900574.

    PubMed 31141631

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Venetoclax in people with Chronic Lymphocytic Leukemia and Recurrent 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 11 inclusion and 14 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 11 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?

Best response (complete response /complete response with incomplete recovery) of combined ibrutinib and venetoclax (time frame: Up to 2 months after treatment). 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 NCT02756897, 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 11 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in