Obinutuzumab and Ibrutinib as Front Line Therapy in Treating Patients With Indolent Non-Hodgkin's Lymphomas

NCT03198026 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 17P.176JT 10049
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Hodgkin's Lymphoma; Ann Arbor Stage II Follicular Lymphoma; Ann Arbor Stage II Nodal Marginal Zone Lymphoma; Ann Abor Stage III B-Cell Non-Hodgkin Lymphoma; Ann Arbor Stage III Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Ann Arbor Stage III Follicular Lymphoma; Ann Arbor Stage III Nodal Marginal Zone Lymphoma; Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma; Ann Arbor Stage IV Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Ann Arbor Stage IV Follicular Lymphoma; Ann Arbor Stage IV Nodal Marginal Zone Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Indolent Non-hodgkin Lymphoma; Stage II Splenic Marginal Zone Lymphoma; Stage III Splenic Marginal Zone Lymphoma; Stage IV Splenic Marginal Zone Lymphoma; Ann Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Outcome Measures

Primary Outcomes (1)

• Overall response rate in patients with newly diagnosed indolent lymphoma requiring treatment, including complete response and partial response

  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.

  Up to 2 years

Secondary Outcomes (8)

• Partial remission or complete remission in patients treated with ibrutinib and obinutuzumab

  Two years

• Progression free survival

  1 year

• Progression free survival

  3 years

• Progression free survival

  5 years

• Overall survival

  1 year

Study Arms (1)

Treatment (ibrutinib, obinutuzumab)

EXPERIMENTAL

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.

Drug: Ibrutinib; Biological: Obinutuzumab; Other: Laboratory Biomarker Analysis

Interventions

Ibrutinib DRUG

Given PO

Also known as: 2-Propen-1-one, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1h-pyrazolo(3,4-d)pyrimidin-1-yl)-1-piperidinyl)-, BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765, 936563-96-1

Treatment (ibrutinib, obinutuzumab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: 949142-50-1, Anti-CD20 Monoclonal Antibody R7159, Gazyva, R7159, RO 5072759, GA-101, GA101, huMAB(CD20), RO-5072759, RO5072759

Treatment (ibrutinib, obinutuzumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib, obinutuzumab)

Eligibility Criteria

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

You may qualify if:

• 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
• All patients should have measurable disease; measurable disease is defined as a lymph node or tumor mass that is \>= 1.5 cm in at least one dimension by computed tomography (CT) or the CT portion of the PET/CT
• Documentation of CD20+ status
• Patients must have an indication for therapy per standard modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria including:
• Symptoms attributable to lymphoma
• B symptoms

You may not qualify if:

• 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:
• Patients with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of detectable serum hepatitis B deoxyribonucleic acid (DNA) viremia are not eligible for this study
• Patients with a positive hepatitis B core antibody but with negative hepatitis B DNA maybe considered for participation, but must agree to receive appropriate anti-hepatitis B viral therapy suppression therapy while on obinutuzumab and have hepatitis B DNA monitored every 4 weeks with real-time polymerase chain reaction (PCR) by the treating physician; these patients should be referred to a hepatologist or gastroenterologist for appropriate monitoring and management
• Hepatitis C: patients with positive hepatitis C serology unless hepatitis C virus (HCV) ribonucleic acid (RNA) is confirmed negative by PCR
• Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment
• Patient is receiving other investigational drugs

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Pharmacyclics LLC.: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Follicular

Interventions

ibrutinib; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ubaldo Martinez-Outschoorn, MD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  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 22, 2017
• First Posted: June 23, 2017
• Study Start: February 20, 2018
• Primary Completion (Estimated): September 11, 2026
• Study Completion (Estimated): February 20, 2032
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)