Phase II, Single Arm, Open Label Multi-center Study of Obinutuzumab and Ibrutinib in the Front Line Treatment of Indolent Non-Hodgkin's Lymphomas
Overview
- Phase
- Phase 2
- Intervention
- Ibrutinib
- Conditions
- Non-Hodgkin's Lymphoma
- Sponsor
- Sidney Kimmel Cancer Center at Thomas Jefferson University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Overall response rate in patients with newly diagnosed indolent lymphoma requiring treatment, including complete response and partial response
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This phase II trial studies how well obinutuzumab and ibrutinib work as front line therapy in treating patients with indolent non-Hodgkin's lymphoma. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab and ibrutinib may work better in treating patients with non-Hodgkin's lymphomas.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the efficacy of the combination of ibrutinib and obinutuzumab in chemotherapy naive patients with indolent lymphomas. SECONDARY OBJECTIVES: I. To assess progression free survival rates and overall survival rates in indolent lymphomas. II. To assess safety and tolerability of the combination. III. To evaluate response using positron emission tomography (PET) and correlate PET negativity with durability of response. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 months after cycle 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses. After completion of study treatment, patients are followed up monthly for 1 year, every 3-6 months for 4 years, and then 1 year later.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Previously untreated, histologically confirmed indolent non-Hodgkin's lymphoma as follows:
- •Follicular lymphoma (World Health Organization \[WHO\] classification grade 1, 2, or 3a)
- •Marginal zone lymphoma including:
- •Nodal and splenic marginal zone lymphoma (MZL) who have an indication for systemic therapy
- •Extranodal MZL:
- •Nongastric/noncutaneous MZL requiring systemic therapy
- •Cutaneous MZL will be eligible only if they have pathologically confirmed extra-cutaneous disease
- •Gastric MZL only if stage IIIE/IV defined as lymph node involvement on both sides of the diaphragm or with disseminated extranodal disease such as bone marrow or additional extra nodal sites
- •Pathological diagnosis should be obtained by incisional or excisional tissue biopsy; core biopsy is permissible if obtaining an incisional or excisional is not possible and if the grade can be assessed on the core biopsy; a core biopsy can also be used if deemed in the best interest of the patient in the opinion of the investigator
- •Patients must have stage II-IV disease
Exclusion Criteria
- •Prior history of malignancies unless the patient has been disease free for \>= 5 years; exceptions include basal cell carcinoma or squamous cell carcinoma of the skin; carcinoma in situ of cervix; carcinoma in situ of breast, localized prostate cancer, or superficial bladder cancer that has undergone curative therapy
- •Prior therapy for lymphoma including chemotherapy or immunotherapy including ibrutinib/anti-CD20 agents; patient may have received corticosteroids, but should be off them 2 weeks prior to study entry; known prior significant hypersensitivity to obinutuzumab (not including infusion reactions) or ibrutinib
- •Patients with evidence of large B cell transformation (transformed disease) are not eligible
- •Known central nervous system (CNS) involvement by lymphoma
- •Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
- •Concomitant use of warfarin or other vitamin K antagonists
- •Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
- •Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of cycle 1
- •Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1) seropositive status
- •Viral hepatitis:
Arms & Interventions
Treatment (ibrutinib, obinutuzumab)
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 months after cycle 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses. After completion of study treatment, patients are followed up monthly for 1 year, every 3-6 months for 4 years, and then annually for up to 2 years.
Intervention: Ibrutinib
Treatment (ibrutinib, obinutuzumab)
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 months after cycle 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses. After completion of study treatment, patients are followed up monthly for 1 year, every 3-6 months for 4 years, and then annually for up to 2 years.
Intervention: Obinutuzumab
Treatment (ibrutinib, obinutuzumab)
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 months after cycle 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses. After completion of study treatment, patients are followed up monthly for 1 year, every 3-6 months for 4 years, and then annually for up to 2 years.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Overall response rate in patients with newly diagnosed indolent lymphoma requiring treatment, including complete response and partial response
Time Frame: Up to 2 years
Response will be assessed by the revised Lugano. Will compute estimates of response, along with corresponding confidence intervals, using appropriate exact methods that take into account the 2-stage design.
Secondary Outcomes
- Partial remission or complete remission in patients treated with ibrutinib and obinutuzumab(Two years)
- Overall survival(5 years)
- Progression free survival(5 years)
- Incidence of grade III-IV toxicity(Two years)
- Progression free survival(1 year)
- Progression free survival(3 years)
- Overall survival(1 year)
- Overall survival(3 years)