Mature B-Cell Non-Hodgkin Lymphoma
Conditions
Keywords
Relapsed, Refractory, Pediatrics, B-NHL
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).
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
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 30 Years
Healthy 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
| Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A) | Up to 3 treatment cycles (cycle length = 21 days) |
| Duration of response (DOR) (Arm B) | 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) | Approximately 3 years |
| Serum concentration of obinutuzumab (Arms A and B) | Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days) |
| Serum concentration of rituximab (Arm A) | Up to 3 treatment cycles (cycle length = 21 days) |
| Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B) | Up to 3 treatment cycles (cycle length = 21 days) |
Countries
Australia, Brazil, China, Czechia, Denmark, France, Germany, Hungary, Italy, Poland, South Korea, Spain, United States
Contacts
CONTACTReference Study ID Number: CO43810 https://forpatients.roche.com/ No attachments to email below.
CONTACTFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-LaRoche
Outcome results
None listed