A Study 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

Phase 1

Conditions: CD20 positive B-Cell Non-Hodgkin Lymphoma
MedDRA version: 23.1Level: LLTClassification code 10084346Term: B-cell non-Hodgkin's lymphomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2021-006326-48-DK

Lead Sponsor: F.Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 65

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-cell non-Hodgkin lymphoma (B-NHL) that expresses CD20 (reconfirmed by immunohistochemistry [IHC]), or flow cytometry if IHC is not possible including Burkitt lymphoma (BL), Burkitt leukemia (BAL) (mature B-cell leukemia fragment antigen-binding [FAB] L3), diffuse large B-cell lymphoma (DLBCL), and primary mediastinal large B-cell lymphoma (PMBCL), at the time of first relapsed or refractory (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
? Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales
? Adequate bone marrow function
? Adequate liver and renal function
? Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
? Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
? Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR test and negative result within 48 hours before study treatment
? Vaccination status in line with the French National guidelines/recommendations (French vaccine strategy council [COSV])
? For female participants of childbearing potential, or who will reach childbearing potential during the study: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 18 months after obinutuzumab pretreatment, 2 months after the final dose of glofitamab, 12 months after the final dose of rituximab and/or ifosfamide, carboplatin, and etoposide (ICE), or 3 months after the final dose of tocilizumab
? For male participants who are expected to reach sexual maturity during the study, or have already reached sexual maturity by the screening visit: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 6 months after the final dose of rituximab and/or ICE, or 2 months after the last dose of tocilizumab (if applicable), whichever is longer, to avoid exposing the embryo
? Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods
Are the trial subjects under 18? yes
Number of subjects for this age range: 55
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

? Isolated CNS disease of mature B-NHL without systemic involvement, and primary central nervous system (CNS) lymphoma
? Receipt of glofitamab prior to study enrollment
? Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade <=1
?Participants with active infections which are not resolved prior to Day 1 of Cycle 1
? Grade >=3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
? Prior solid organ transplantation
? Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
? Known or suspected 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
? 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
? Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Exclusion criteria applicable to Cohort A only
? Receipt of any R-ICE chemoimmunotherapy prior to study enrollment into Cohort A
? Receipt of more than one prior line of standard-of-care B-NHL chemoimmunotherapy
? Prior allogeneic or autologous stem cell transplantation (SCT)
Exclusion criteria applicable to Cohort B only
? Prior treatment with systemic chemotherapy and immunotherapeutic anticancer agents
? Patients with uncontrolled CNS involvement
? Prior allogeneic or autologous SCT <=100 days post-transplant prior to enrollment
? Presence of Grade >=2 acute or extensive chronic graft -versus-host disease (GVHD) in participants who received prior allogeneic hematopoietic stem cell transplantation (HSCT)
?Prior treatment with systemic immunosuppressive agents for treatment of GVHD, within 4 weeks or five half-lives of the drug, whichever is shorter, before Cycle 1 Day 1

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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