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RecruitingInterventionalPhase 1/Phase 2

A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

NCT ID: NCT05533775Sponsor: Hoffmann-La RocheLast updated: 2026-06-03

Summary

The purpose of this study is to evaluate the safety and efficacy of glofitamab, as monotherapy and in combination with a standard chemoimmunotherapy regimen: rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in pediatric and young adult participants with relapsed and refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL).

Arms & interventions

  • DrugObinutuzumab

    Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)

  • DrugGlofitamab

    Arm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3 Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter (Cycle length = 21 days)

  • DrugRituximab

    Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

  • DrugIfosfamide

    Participants will receive IV ifosfamide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

  • DrugCarboplatin

    Participants will receive IV carboplatin on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

  • DrugEtoposide

    Participants will receive IV etoposide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

  • DrugTocilizumab

    Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events

Outcome measures

Primary

  • Achievement of a complete response (CR) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (Arm A)

    Time frame: Up to 3 treatment cycles (cycle length = 21 days)

  • Percentage of participants with adverse events (AEs) (Arm A)

    Time frame: Approximately 3 years

  • Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)

    Time frame: Up to 3 treatment cycles (cycle length = 21 days)

  • Serum concentration of glofitamab monotherapy (Arm B)

    Time frame: Up to 12 treatment cycles (Arm B) (cycle length = 21 days)

Secondary

  • Objective response rate (ORR) (Arms A and B)

    Time frame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)

  • Duration of complete response (DOCR) (Arm A)

    Time frame: From the first occurrence of a documented complete response (CR) to documented disease progression or death from any cause (whichever occurs first) (approximately 3 years)

  • Progression-free survival (PFS) (Arm A)

    Time frame: From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 3 years)

  • Event-free survival (EFS) (Arm A)

    Time frame: From enrollment to the first occurrence of disease progression, death from any cause, or start of new anti-lymphoma therapy (not including planned hematopoietic stem cell transplantation (HSCT)) (approximately 3 years)

  • Overall survival (OS) (Arms A and B)

    Time frame: From enrollment to the date of death from any cause (Arm A = approximately 3 years, Arm B = approximately 4 years)

  • Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A)

    Time frame: Up to 3 treatment cycles (cycle length = 21 days)

  • Duration of response (DOR) (Arm B)

    Time frame: From the first occurrence of a documented CR or partial response (PR) until documented disease progression or death from any cause, whichever occurs first (approximately 4 years)

  • Percentage of participants with AEs (arm B)

    Time frame: Approximately 3 years

  • Serum concentration of obinutuzumab (Arms A and B)

    Time frame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)

  • Serum concentration of rituximab (Arm A)

    Time frame: Up to 3 treatment cycles (cycle length = 21 days)

  • Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)

    Time frame: Up to 3 treatment cycles (cycle length = 21 days)

Eligibility criteria

Sex: AllAge: 6 Months to 30 YearsHealthy volunteers: No
Inclusion Criteria: * Age 6 months to \< 18 years at the time of signing Informed Consent for Cohort A Part 1 and Cohort B of the study, and age 6 months to \< 30 years old at the time of signing Informed Consent for Cohort A Part 2 of the study * Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC or flow cytometry if IHC is not possible), including BL, BAL (mature B-cell leukemia FAB L3), DLBCL, and PMBCL, at the time of first R/R disease for Cohort A and second or greater R/R disease for Cohort B * Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B * Measurable disease, defined as: At least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or at least one bi dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension; or percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates * Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales: Participants \< 16 years old: Lansky Performance Status ≥ 50%; Participants ≥ 16 years old: Karnofsky Performance Status ≥ 50% * Adequate bone marrow, liver, and renal function * Negative test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV) * Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count ≥200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months * Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment * Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods Exclusion Criteria: * Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma * Receipt of glofitamab prior to study enrollment * Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade ≤ 1 (exceptions: alopecia, Grade 2 peripheral neuropathy) * Grade ≥ 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy * Participants with active infections which are not resolved prior to Day 1 of Cycle 1 * Prior solid organ transplantation * Known or suspected history of hemophagocytic lymphohistiocytosis (HLH), or chronic active Epstein-Barr viral infection (CAEBV) * Active autoimmune disease requiring treatment * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products, except if the participant was able to safely receive it after initial administration (consider consultation with Medical Monitor) * History of confirmed progressive multifocal leukoencephalopathy * Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease * Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results * Major surgery or significant traumatic injury \< 28 days prior to the obinutuzumab pretreatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment * Administration of a live, attenuated vaccine within 4 weeks before the start of study treatment (obinutuzumab pretreatment) or at any time during the study treatment period and within 12 months after end of study treatment * Participants with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug

Study locations (10)

Children's Hospital of Alabama

Birmingham, Alabama, 35233

Recruiting

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609

Recruiting

Kaiser Permanente Oakland Medical Center

Oakland, California, 94611

Recruiting

Kaiser Permanente - Roseville

Roseville, California, 95661

Recruiting

Kaiser Permanente - Santa Clara

Santa Clara, California, 95051

Recruiting

Johns Hopkins University

Baltimore, Maryland, 21231

Recruiting

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Childrens Mercy Hosp & Clinics

Kansas City, Missouri, 64108

Recruiting

MSKCC

New York, New York, 10065

Recruiting

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

Recruiting