Maintenance Obinutuzumab in Treating Patients With Central Nervous System Lymphoma Who Have Achieved a Complete or Partial Response

NCT06175000 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PHS-OB-PCNSL-01ML29496
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 7

Brief Summary

This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved the disappearance of all signs of cancer in response to treatment (complete response) or a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment (partial response). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Conditions

Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (1)

• Partial response (PR) or complete response (CR) duration

  PR or CR duration will be assessed using Kaplan-Meier product limit estimates and compared between patients with maintenance versus without obinutuzumab maintenance using the log-rank test. In addition, the Cox proportional hazard model will be used to estimate hazard ratios.

  From the date of brain magnetic resonance imaging (MRI) after completion of first-line treatment which confirms PR or CR, to disease progression or death, assessed up to 2 years

Secondary Outcomes (10)

• Overall survival (OS) after CR

  From the date of brain MRI after completion of first-line treatment which confirms PR or CR, to death, assessed up to 2 years

• Neurocognitive function - Wechsler Adult Intelligence Scale

  Up to 2 years

• Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain Neoplasm 20-item

  Up to 2 years

• Progression free survival (PFS)

  From the start date of first-line primary central nervous system lymphoma (PCNSL) treatment to disease progression or death, assessed up to 2 years

• Overall survival

  From the start date of first-line PCNSL treatment to death, assessed up to 2 years.

Study Arms (2)

Arm I (obinutuzumab

EXPERIMENTAL

Patients receive obinutuzumab IV on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles, and on day 1 for the subsequent cycles. Cycles repeat every 60 days for 2 years in the absence of disease progression or unacceptable toxicity.

Procedure: Cognitive Assessment; Biological: Obinutuzumab; Other: Quality of Life Assessment

Arm II (observation)

ACTIVE COMPARATOR

Patients undergo observation for a total of 2 years.

Procedure: Cognitive Assessment; Other: Quality of Life Assessment

Interventions

Cognitive Assessment PROCEDURE

Ancillary studies to evaluate neurocognitive function at study entry and at 2 years after study entry.

Arm I (obinutuzumab; Arm II (observation)

Obinutuzumab BIOLOGICAL

Given IV

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

Arm I (obinutuzumab

Quality of Life Assessment OTHER

Ancillary studies to evaluate quality of life at study entry and at 2 years after study entry.

Arm I (obinutuzumab; Arm II (observation)

Eligibility Criteria

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

You may qualify if:

• CD20+ B-cell primary central nervous system lymphoma (PCNSL) confirmed at the time of diagnosis by histology, cytology, or immunocytochemistry from cerebrospinal fluid (CSF); diagnosis must be documented by pathology report.
• Must have undergone first-line treatment with a high-dose methotrexate-based chemotherapy regimen with or without brain radiotherapy; high-dose methotrexate is defined as \>= 3 grams/m\^2; methotrexate dose reduction for creatinine clearance \< 100 ml/min is permitted
• Must be within 75 days of completion of first-line treatment regimen at the time of randomization; must have achieved objective response (PR or CR/unconfirmed complete response \[CRu\]) to first-line treatment
• Brain magnetic resonance imaging (MRI) documenting objective response must be obtained within 30 days before randomization
• If CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or a slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; Note: CR requires complete disappearance of all enhancing abnormalities on gadolinium-enhanced MRI; if CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; for CRu, some patients will have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; it is often difficult to ascertain whether this represents a residual nidus of tumor or scar tissue; if the abnormality does not change or slowly involutes without therapy and corticosteroids, it is reasonable to categorize as a CRu; at the time CR/CRu is determined, the patient should not have used corticosteroids for at least two weeks
• Karnofsky performance status (KPS) \>= 60; Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
• Signed informed consent form (ICF)
• Ability and willingness to comply with the requirements of the study protocol
• Total bilirubin \< 3 x the upper limit of normal (ULN), ≤ 7 days before date of randomization
• Creatinine clearance \> 30 mL/min (calculated according to institutional standards or using Cockcroft-Gault formula), ≤ 7 days before date of randomization
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 5 x ULN, ≤7 days before date of randomization
• Platelet ≤ 75,000 cells/mm\^3, ≤ 7 days before date of randomization
• Hemoglobin \> 9 g/dL, ≤ 7 days before date of randomization
• Absolute neutrophil count \> 1.5 x 10\^3 cells/mm\^3, ≤ 7 days before date of randomization
• Surgically sterile or agree to use effective contraception using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly while receiving obinutuzumab and \>= 18 months after the last dose of obinutuzumab for women, and 180 days after the last dose of obinutuzumab for men

You may not qualify if:

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Clinical evidence of extra-central nervous system (CNS) (systemic) non-Hodgkin lymphoma
• Known hypersensitivity to any of the study drugs
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible; patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for \>= 2 years prior to randomization
• 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 prior to study randomization
• Major surgery within 4 weeks prior to study randomization
• Known infection with human immunodeficiency virus (HIV)
• Positive hepatitis serologies:
• Women who are pregnant or lactating
• Vaccination with a live vaccine a minimum of 4 weeks prior to study randomization

Sponsors & Collaborators

• Providence Health & Services: lead

Study Sites (7)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

Providence Health & Services; Providence Neurological Specialties

Portland, Oregon, 97225, United States

RECRUITING

Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

RECRUITING

University of Vermont

Burlington, Vermont, 05405, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Ivy Center for Advanced Brain Tumor Treatment; Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

RECRUITING

MeSH Terms

Interventions

Mental Status and Dementia Tests; obinutuzumab

Intervention Hierarchy (Ancestors)

Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Prakash Ambady, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tiffany Gervasi-Follmar

CONTACT

503-216-1023; tiffany.gervasi-follmar@providence.org

Holly Rittenberry

CONTACT

503-216-1034; Holly.Rittenberry@providence.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Single
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: December 18, 2023
• Study Start: March 13, 2024
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2029
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)