a study to evaluate glofitamab monotherapy and glofitamab + chemoimmunotherapy in pediatric and young adult participants with relapsed/refractory mature b-cell non-hodgkin lymphoma

Conditions: Mature B-Cell Non-Hodgkin Lymphoma

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).


Eligibility criteria:
inclusion criteria: * age 6 months to \< 18 years at the time of signing informed consent for part 1 and cohort b of the study, and age 6 months to ≤ 30 years old at the time of signing informed consent for 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

Keywords: relapsed refractory pediatrics b-nhl