Glofitamab With Obinutuzumab Pre-treatment for the Treatment of Central Nervous System Lymphoma

NCT06922604 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 24487NCI-2025-02019P30CA033572
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety and side effects of glofitamab after pre-treatment with obinutuzumab and how well they work in treating patients with central nervous system (CNS) lymphoma. Glofitamab is a bispecific antibody that can bind to two different antigens (substances that cause the body to make a specific immune response) at the same time. Glofitamab binds to CD20 on lymphoma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Obinutuzumab can also be administered as a pre-treatment to make glofitamab safer and more tolerable. Giving glofitamab with obinutuzumab pre-treatment may be safe, tolerable, and/or effective in treating patients with CNS lymphoma.

Conditions

Primary Central Nervous System Lymphoma; Secondary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (8)

• Incidence of grade 3 or higher non-hematologic toxicity that does not resolve to grade 1 or better within 7 days

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of grade 3 or 4 thrombocytopenia associated with grade >= 3 bleeding

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of grade 4 neutropenia or grade 4 thrombocytopenia (without clinically significant bleeding) that lasts > 14 days

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of grade >= 3 cytokine release syndrome (CRS) not resolving to grade 1 or better within 7 days

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of grade 4 CRS

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of any emergent grade 3 neurologic toxicity

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of emergent grade 4 neurologic toxicity

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

• Incidence of any grade 5 toxicity

  For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided. Observed toxicities will be summarized by type, severity, and attribution.

  During first 2 cycles of treatment (cycle length = 21 days)

Secondary Outcomes (7)

• Overall response rate (ORR)

  From start of protocol therapy to disease progression and/or start of other anti-lymphoma therapy, assessed up to 24 months

• CR rate

  From start of protocol therapy to disease progression and/or start of other anti-lymphoma therapy, assessed up to 24 months

• Duration of response (DOR)

  From first achievement of PR or CR to time of progression, relapse, or death, whichever is earlier, assessed up to 24 months

• Duration of CR (DOCR)

  From first achievement of CR to time of progression, relapse or death, whichever is earlier, assessed up to 24 months

• Progression-free survival (PFS)

  From start of protocol treatment to time of progression, relapse, or death due to any cause, whichever occurs earlier, assessed up to 24 months

Study Arms (1)

Treatment (obinutuzumab, glofitamab)

EXPERIMENTAL

Patients receive obinutuzumab IV on day 1 of cycle 1 and glofitamab IV over 2-4 hours on days 8 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT at screening and CSF and blood sample collection, brain MRI throughout the study. Patients with secondary CNS lymphoma also undergo CT or PET/CT throughout the study. Additionally, patients with baseline CSF involvement, may undergo lumbar puncture throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Glofitamab; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Biological: Obinutuzumab; Procedure: Positron Emission Tomography

Interventions

Biospecimen Collection PROCEDURE

Undergo CSF and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (obinutuzumab, glofitamab)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (obinutuzumab, glofitamab)

Glofitamab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody RO7082859, Columvi, Glofitamab-gxbm, RO 7082859, RO-7082859, RO7082859

Treatment (obinutuzumab, glofitamab)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (obinutuzumab, glofitamab)

Magnetic Resonance Imaging PROCEDURE

Undergo brain MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (obinutuzumab, glofitamab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA 101, GA-101, GA101, Gazyva, huMAB(CD20), R 7159, R-7159, R7159, RO 5072759, RO-5072759, RO5072759

Treatment (obinutuzumab, glofitamab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (obinutuzumab, glofitamab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Karnofsky performance status (KPS) ≥ 30
• Histologically confirmed primary or secondary CNS lymphoma. Tumor must be positive for CD20 by immunohistochemistry or flow cytometry on the most recent biopsy. Neuroimaging alone is acceptable in secondary CNS lymphoma cases where all of the following criteria are met: 1) brain MRI findings are consistent with CNS lymphoma, 2) the disease has been histologically documented in other sites, 3) the CNS lesions are concomitant with systemic progression, and 4) a brain biopsy would be unadvised per the treating provider.
• Cohort 1: Primary CNS lymphoma
• Cohort 2: Secondary CNS lymphoma
• Patients must not require urgent treatment initiation due to bulky or rapidly progressing CNS lymphoma that poses risk for impending critical brain failure. This includes \> 5 mm of midline shift, radiographic evidence of impending brain herniation, or clinical evidence of significantly increased intracranial pressure such as papilledema
• Have failed methotrexate-based therapy or are ineligible/refuse high-dose methotrexate treatment (e.g. creatinine clearance \[CrCl\] \< 50 mL/min, effusions, ascites etc)
• Measurable CNS lymphoma based on gadolinium enhancement of brain or spine MRI and/or positive CSF or intravitreal fluid cytology
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• Alert and able to participate in a full neurological exam
• Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3

You may not qualify if:

• Contraindication to any of the individual components of glofitamab or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Prior solid organ transplantation
• Prior treatment with systemic immunotherapeutic agents, including but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (mAbs) (e.g., anti cytotoxic T lymphocyte associated protein 4, anti PD-1, and anti PD-L1) within 2 weeks or five half-lives of the drug, whichever is shorter, prior to day 1 of protocol therapy
• Prior treatment with glofitamab or other CD20 x CD3 bispecific antibodies
• Prior use of systemic chemotherapy within 2 weeks of the start of cycle 1
• Prior treatment with intrathecal chemotherapy within 1 week of the start of cycle 1. Note, in patients with lymphoma restricted to the CSF and no other measurable sites of CNS disease, positive CSF cytology must be documented following the most recent administration of intrathecal chemotherapy
• Prior treatment with radiotherapy within 2 weeks prior to day 1 of protocol therapy
• If patients have received radiotherapy within 4 weeks prior to day 1 of protocol therapy, patients must have at least one measurable lesion outside of the radiation field. Patients who have only one measurable lesion that was previously irradiated but subsequently progressed are eligible
• Prior treatment with chimeric antigen receptor T cell (CAR-T) therapy within 30 days prior to day 1 of protocol therapy
• Any investigational therapy for the purposes of treating cancer within 21 days prior to the start of cycle 1
• Corticosteroid use for purposes other than lymphoma symptom control
• The use of inhaled corticosteroids is permitted
• The use of mineralocorticoids for management of orthostatic hypotension is permitted.
• The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
• Participants who require lymphoma symptom control during screening may receive steroids in the following manner:

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; glofitamab; Spinal Puncture; Magnetic Resonance Spectroscopy; obinutuzumab

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• James Godfrey

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 10, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): January 2, 2029
• Study Completion (Estimated): January 2, 2029
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)