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Ann Arbor Stage II Follicular LymphomaPhase 2NCT04450173

Obinutuzumab, Ibrutinib, and Venetoclax for the Treatment of Previously Untreated Stage II-IV Follicular Lymphoma

A Phase 2 study testing Ibrutinib, Obinutuzumab and Venetoclax in people with Ann Arbor Stage II Follicular Lymphoma and Ann Arbor Stage III Follicular Lymphoma, run by University of California, Davis at 4 sites in United States.

Active, not recruiting

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

Official record
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Trial summary

This phase II trial studies how well obinutuzumab, ibrutinib, and venetoclax work in treating patients with previously untreated stage II-IV follicular lymphoma. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Obinutuzumab and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
4 sitesUnited States
Study dates
24 Feb 2021to Apr 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

  • A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated
  • Able and willing to provide written informed consent and to comply with the study protocol
  • Bi-dimensionally measurable disease, with at least one mass lesion >= 2 cm in longest diameter by CT, PET/CT, and/or magnetic resonance imaging (MRI)
  • Must be in need of therapy as evidenced by at least one of the following criteria:
  • Bulky disease defined as:
  • A nodal or extranodal (except spleen) mass > 7 cm in its greater diameter or,
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  • At least 3 nodal or extranodal sites >= 3 cm in diameter
  • Presence of at least one B symptom:
  • Fever (> 38 Celsius [C]) not due to infectious etiology
  • Night sweats
  • Weight loss > 10% in the past 6 months
  • Fatigue due to lymphoma
  • Splenomegaly (> 13 cm)
  • Compression syndrome (ureteral, orbital, gastrointestinal)
  • Any of the following cytopenias, due to lymphoma:
  • Hemoglobin =< 10 g/dL
  • Platelets =< 100 x 10^9/L
  • Absolute neutrophil count (ANC) < 1.5 x 10^9/L
  • Pleural or peritoneal effusion
  • Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta (B)2 microglobulin > ULN
  • Other lymphoma-mediated symptoms as determined by the treating physician
  • Stage II, III, or IV disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count (ANC) > 1.0 x 10^9/L
  • Platelet count > 50 x 10^9/L
  • Prothrombin time (PT)/international normal ratio (INR) < 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonists, then INR =< 3.0)
  • Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN)
  • Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
  • Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
  • Women of childbearing potential and men who are sexually active must practice reliable contraceptive measures started at least 4 weeks before study therapy and continued for 18 months following discontinuation of therapy. Females of childbearing potential must either completely abstain from heterosexual sexual contact or must use 2 methods of reliable contraception. Reliable contraceptive methods include 1 highly effective method (intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants) and at least 1 additional method (condom, diaphragm, or cervical cap) every time they have sex with a male. Males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential. Men must agree to not donate sperm during and for 90 days after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study

Who cannot join

  • Known active central nervous system lymphoma or leptomeningeal disease
  • Follicular lymphoma with evidence of diffuse large B-cell transformation
  • Grade 3b follicular lymphoma
  • Any prior history of other malignancy besides follicular lymphoma, unless the patient has been free of disease for >= 5 years and felt to be at low risk for recurrence by the treating physician, except:
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
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  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (e.g., patients in whom dosing with obinutuzumab would be contraindicated for safety reasons)
  • Known history of human immunodeficiency virus (HIV), active hepatitis C virus, active hepatitis B virus infection, or known bacterial, viral, fungal, mycobacterial, parasitic active systemic infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to the start of cycle 1
  • Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated
  • Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML), positive test results for human T-lymphotropic 1 virus, or suspected active or latent tuberculosis
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
  • Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block. QT prolongation is not a significant ECG abnormality that would warrant exclusion
  • Female subjects who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 90 days of last dose of study drug. Male subjects who plan to father a child while enrolled in this study or within 90 days after the last dose of study drug
  • Administration of any investigational agent within 28 days of first dose of study drug
  • Patients who have undergone major surgery within 14 days
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
  • Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Subjects with chronic liver disease and hepatic impairment meeting Child-Pugh class C
  • Subjects who received a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitor or inducer
  • Unwilling or unable to participate in all required study evaluations and procedures
  • Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of California, San Francisco (UCSF) Fresno

    Fresno, California, 93701

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • University of California, San Diego

    San Diego, California, 92037

Other trials in United States

About this study

Official title: A Phase II Trial of the Combination of Obinutuzumab, Ibrutinib, and Venetoclax in Patients With Previously Untreated Follicular Lymphoma

This phase II trial studies how well obinutuzumab, ibrutinib, and venetoclax work in treating patients with previously untreated stage II-IV follicular lymphoma. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Ibrutinib and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab, ibrutinib, and venetoclax together may work better in treating follicular lymphoma compared to each drug alone.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the efficacy of obinutuzumab combined with venetoclax and ibrutinib in patients with previously untreated follicular lymphoma (FL) (determined by a positron emission tomography [PET]/computed tomography [CT] complete response [CR] rate at 12 months as per International Workshop Lymphoma Response Criteria, Cheson 2014).

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of obinutuzumab in combination with venetoclax and ibrutinib in patients with untreated FL as assessed by frequency, severity, and relatedness of treatment-emergent adverse events (AEs) as well as frequency of treatment-emergent AEs requiring discontinuation or dose reduction of study drug.

II. To evaluate the efficacy of obinutuzumab in combination with venetoclax and ibrutinib in subjects with untreated FL as assessed by CR at 30 months, overall response rate (ORR) (CR + partial response [PR]), duration of response (DOR), time to next anti-lymphoma treatment (TTNT), progression-free survival (PFS), and OS.

OUTLINE:

Patients receive obinutuzumab intravenously (IV) over 60 minutes on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, and 24. Patients also receive venetoclax orally (PO) once daily (QD) on days 1-28 (days 4-28 of cycle 1) and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years.

Medical subject headings
Lymphoma, Follicular

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

  • ObinutuzumabBiological

    Also called Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva

    Given IV

  • VenetoclaxDrug

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

    Given PO

Study groups in NCT04450173
Study groupRoleWhat they receive
Treatment (obinutuzumab, venetoclax, ibrutinib)ExperimentalPatients receive obinutuzumab IV over 60 minutes on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, and 24. Patients also receive venetoclax PO QD on days 1-28 (days 4-28 of cycle 1) and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Ibrutinib; Biological: Obinutuzumab; Drug: Venetoclax

What is being measured

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

  1. Complete response (CR) rate

    Determined by positron emission tomography (PET)/computed tomography (CT) based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.

    Measured: At 12 months

Secondary outcomes (8)

  1. Frequency, severity, and relatedness of treatment-emergent adverse events (AEs)

    Adverse events will be graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity data by type and severity will be summarized by frequency tables.

    Measured: Up to 30 days after completion of study treatment

  2. Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions

    Adverse events will be graded and recorded according to NCI CTCAE version 5.0. Toxicity data by type and severity will be summarized by frequency tables.

    Measured: Up to 30 days after completion of study treatment

  3. CR rate

    Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. The number and percentage of subjects with a CR will be tabulated.

    Measured: At 30 months (120 weeks)

  4. Overall response rate (ORR)

    CR + partial response (PR), determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded.

    Measured: Up to 2 years after completion of study treatment

  5. Duration of response

    CR + PR, determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval (CI).

    Measured: From the time by which measurement criteria for CR or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 2 years after completion of study treatment

  6. Time to next anti-lymphoma treatment

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the date of cycle 1/day 1 (each cycle is 28 days) to the date of first documented new anti-lymphoma treatment or death from any cause, assessed up to 2 years after completion of study treatment

  7. Progression-free survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the date of cycle 1/day 1 (each cycle is 28 days) to the date of first documented progression or death, assessed up to 2 years after completion of study treatment

  8. Overall survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.

    Measured: From the date of cycle 1/day 1 (each cycle is 28 days) to the date of death regardless of cause, assessed up to 2 years after completion of study treatment

Timeline

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

  1. First posted29 Jun 2020
  2. Study start24 Feb 2021
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 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
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04450173
Sponsor's protocol ID
UCDCC#275
Other IDs
NCI-2020-01372, UCDCC#275, P30CA093373
Status last verified
Apr 2026
First submitted
12 Jun 2020
Last updated
13 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib, Obinutuzumab and Venetoclax in people with Ann Arbor Stage II Follicular Lymphoma and Ann Arbor Stage III Follicular Lymphoma, run by University of California, Davis 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 32 inclusion and 23 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 13 Apr 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?

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?

Complete response (CR) rate (time frame: At 12 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 NCT04450173.

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 13 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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