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

NCT05533775 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CO43810
• Study Type: interventional
• Target: 65
• Locations: 13 countries
• Sites: 28

Brief 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).

Conditions

Mature B-Cell Non-Hodgkin Lymphoma

Keywords

Relapsed; Refractory; Pediatrics; B-NHL

Outcome Measures

Primary Outcomes (4)

• 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)

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

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

  Approximately 3 years

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

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

• Serum concentration of glofitamab monotherapy (Arm B)

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

Secondary Outcomes (11)

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

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

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

  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)

  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)

  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)

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

Study Arms (2)

Arm A

EXPERIMENTAL

Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).

Drug: Obinutuzumab; Drug: Glofitamab; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: Tocilizumab

Arm B

EXPERIMENTAL

Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).

Drug: Obinutuzumab; Drug: Glofitamab; Drug: Tocilizumab

Interventions

Obinutuzumab DRUG

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

Arm A; Arm B

Glofitamab DRUG

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)

Arm A; Arm B

Rituximab DRUG

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

Arm A

Ifosfamide DRUG

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)

Arm A

Carboplatin DRUG

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)

Arm A

Etoposide DRUG

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)

Arm A

Tocilizumab DRUG

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

Arm A; Arm B

Eligibility Criteria

• Age: 6 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (28)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Kaiser Permanente Oakland Medical Center

Oakland, California, 94611, United States

RECRUITING

Kaiser Permanente - Roseville

Roseville, California, 95661, United States

RECRUITING

Kaiser Permanente - Santa Clara

Santa Clara, California, 95051, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21231, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Childrens Mercy Hosp & Clinics

Kansas City, Missouri, 64108, United States

RECRUITING

MSKCC

New York, New York, 10065, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Queensland Children?s Hospital

South Brisbane, Queensland, 4101, Australia

RECRUITING

Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

RECRUITING

Hospital Erasto Gaertner

Curitiba, Paraná, 81520-060, Brazil

RECRUITING

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

São Paulo, São Paulo, 04023-062, Brazil

RECRUITING

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

RECRUITING

Fakultni nemocnice v Motole;Klinika detske hematologie a onkologie

Prague, 150 06, Czechia

RECRUITING

Rigshospitalet

København Ø, 2100, Denmark

RECRUITING

Hôpital Pellegrin

Bordeaux, 33076, France

RECRUITING

Gustave Roussy

Villejuif, 94800, France

RECRUITING

Universitaetsklinikum Muenster

Münster, 48149, Germany

RECRUITING

Semmelweis Egyetem II. sz. Gyermekgyogyaszati Klinika

Budapest, 1097, Hungary

RECRUITING

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 00165, Italy

RECRUITING

Ospedaliera Ospedale Infantile Regina Margherita

Turin, Piedmont, 10126, Italy

RECRUITING

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

Wroclaw, 50-556, Poland

RECRUITING

Seoul National University Hospital- Pediatric Site

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesus

Madrid, 28009, Spain

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

obinutuzumab; glofitamab; Rituximab; Ifosfamide; Carboplatin; Etoposide; tocilizumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Clinical Trials

  Hoffmann-LaRoche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: CO43810 https://forpatients.roche.com

CONTACT

888-662-6728; global-roche-genentech-trials@gene.com

Study Design

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

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 9, 2022
• Study Start: November 16, 2022
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2032
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (2); CZ (1); BR (2); DK (1); FR (2); DE (1); HU (1); PL (1); CN (1); US (10); AU (2); ES (2); IT (2)