A Phase II Trial of the Combination of Obinutuzumab, Ibrutinib, and Venetoclax in Patients With Previously Untreated Follicular Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Ibrutinib
- Conditions
- Ann Arbor Stage II Follicular Lymphoma
- Sponsor
- University of California, Davis
- Enrollment
- 40
- Locations
- 6
- Primary Endpoint
- Complete response (CR) rate
- Status
- Active, not recruiting
- Last Updated
- 19 days ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVE: I. 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: I. 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.
Investigators
Joseph Tuscano
Principal Investigator
University of California, Davis
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Treatment (obinutuzumab, venetoclax, ibrutinib)
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.
Intervention: Ibrutinib
Treatment (obinutuzumab, venetoclax, ibrutinib)
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.
Intervention: Obinutuzumab
Treatment (obinutuzumab, venetoclax, ibrutinib)
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.
Intervention: Venetoclax
Outcomes
Primary Outcomes
Complete response (CR) rate
Time Frame: At 12 months
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.
Secondary Outcomes
- 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)
- Overall survival(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)
- Frequency, severity, and relatedness of treatment-emergent adverse events (AEs)(Up to 30 days 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)
- Time to next anti-lymphoma treatment(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)
- Progression-free survival(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)