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

NCT04450173 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: UCDCC#275NCI-2020-01372P30CA093373
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Ann Arbor Stage III Follicular Lymphoma; Ann Arbor Stage IV Follicular Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Ann Arbor Stage II Follicular Lymphoma

Outcome Measures

Primary Outcomes (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.

  At 12 months

Secondary Outcomes (8)

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

  Up to 30 days after completion of study treatment

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

  Up to 30 days after completion of study treatment

• CR rate

  At 30 months (120 weeks)

• Overall response rate (ORR)

  Up to 2 years after completion of study treatment

• Duration of response

  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

Study Arms (1)

Treatment (obinutuzumab, venetoclax, ibrutinib)

EXPERIMENTAL

Patients 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.

Drug: Ibrutinib; Biological: Obinutuzumab; Drug: Venetoclax

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (obinutuzumab, venetoclax, ibrutinib)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (obinutuzumab, venetoclax, ibrutinib)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (obinutuzumab, venetoclax, ibrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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:

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Pharmacyclics LLC.: collaborator
• Genentech, Inc.: collaborator
• University of California, Davis: lead

Study Sites (4)

University of California, San Francisco (UCSF) Fresno

Fresno, California, 93701, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of California, San Diego

San Diego, California, 92037, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

ibrutinib; obinutuzumab; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Joseph M Tuscano

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: June 29, 2020
• Study Start: February 24, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (4)