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NCT05533775PHASE1, PHASE2Recruiting

A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Hoffmann-La Roche

Start Date

11/16/2022

Completion Date

11/30/2032

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

Age Range: No minimum to 30 years

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

Interventions

DRUG

Obinutuzumab

DRUG

Glofitamab

DRUG

Rituximab

DRUG

Ifosfamide

DRUG

Carboplatin

DRUG

Etoposide

DRUG

Tocilizumab

Interested in This Trial?

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Conditions

Mature B-Cell Non-Hodgkin Lymphoma

Locations

Children's Hospital of Alabama

Birmingham, Alabama 35233

United States

UCSF Benioff Children's Hospital Oakland

Oakland, California 94609

United States

Kaiser Permanente Oakland Medical Center

Oakland, California 94611

United States

Kaiser Permanente - Roseville

Roseville, California 95661

United States

Kaiser Permanente - Santa Clara

Santa Clara, California 95051

United States

Johns Hopkins University

Baltimore, Maryland 21231

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Childrens Mercy Hosp & Clinics

Kansas City, Missouri 64108

United States

MSKCC

New York, New York 10065

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

Queensland Children?s Hospital

South Brisbane, Queensland 4101

Australia

Perth Children's Hospital

Nedlands, Western Australia 6009

Australia

Hospital Erasto Gaertner

Curitiba, Paraná 81520-060

Brazil

Graacc-Grupo de Apoio ao adolescente e a crianca com cancer

São Paulo, São Paulo 04023-062

Brazil

West China Second University Hospital

Chengdu, 610041

China

Sun Yet-sen University Cancer Center

Guangzhou, 510060

China

Guangxi Cancer Hospital of Guangxi Medical University

Nanning, 530201

China

Fakultni nemocnice v Motole;Klinika detske hematologie a onkologie

Prague, 150 06

Czechia

Rigshospitalet

København Ø, 2100

Denmark

Hôpital Pellegrin

Bordeaux, 33076

France

Gustave Roussy

Villejuif, 94800

France

Universitaetsklinikum Muenster

Münster, 48149

Germany

Semmelweis Egyetem II. sz. Gyermekgyogyaszati Klinika

Budapest, 1097

Hungary

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, Lazio 00165

Italy

Ospedaliera Ospedale Infantile Regina Margherita

Turin, Piedmont 10126

Italy

Ponadregionalne Centrum Onkologii Dzieci?cej ,,Przyladek Nadziei?;Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej we Wroclawiu

Wroclaw, 50-556

Poland

Seoul National University Hospital- Pediatric Site

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital Infantil Universitario Niño Jesus

Madrid, 28009

Spain