A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Phase 1
Recruiting
- Conditions
- Mature B-Cell Non-Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT05533775
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- 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-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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Etoposide Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm A Carboplatin Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm A Obinutuzumab Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm A Glofitamab Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm B Obinutuzumab Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days). Arm A Rituximab Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm A Ifosfamide Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm A Tocilizumab Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). Arm B Tocilizumab Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days). Arm B Glofitamab Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Objective response rate (ORR) (Arms A and B) Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days) 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) 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) Serum concentration of rituximab (Arm A) Up to 3 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) Overall survival (OS) (Arms A and B) From the first study treatment to the date of death from any cause (Arm A = approximately 3 years, Arm B = 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) Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B) Up to 3 treatment cycles (cycle length = 21 days)
Trial Locations
- Locations (24)
Graacc-Grupo de Apoio ao adolescente e a crianca com cancer
🇧🇷Sao Paulo, São Paulo, Brazil
Rigshospitalet
🇩🇰København Ø, Denmark
Hôpital Pellegrin
🇫🇷Bordeaux, France
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
IRCCS Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Lazio, Italy
Ospedaliera Ospedale Infantile Regina Margherita
🇮🇹Torino, Piemonte, Italy
Hospital Infantil Universitario Niño Jesus
🇪🇸Madrid, Spain
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente Oakland Medical Center
🇺🇸Oakland, California, United States
Kaiser Permanente - Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente - Santa Clara
🇺🇸Santa Clara, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Childrens Mercy Hosp & Clinics
🇺🇸Kansas City, Missouri, United States
MSKCC
🇺🇸New York, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Queensland Children?s Hospital
🇦🇺South Brisbane, Queensland, Australia
Perth Children's Hospital
🇦🇺Nedlands, Western Australia, Australia
Hospital Erasto Gaertner
🇧🇷Curitiba, Paraná, Brazil
Gustave Roussy
🇫🇷Villejuif CEDEX, France
Seoul National University Hospital- Pediatric Site
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain