A Phase I/II, Open-Label, Single-Arm, Two-Part Trial 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
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).
Arms & 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
Outcome measures
Primary
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)
Time frame: Up to 3 treatment cycles (cycle length = 21 days)
Percentage of participants with adverse events (AEs) (Arm A)
Time frame: Approximately 3 years
Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)
Time frame: Up to 3 treatment cycles (cycle length = 21 days)
Serum concentration of glofitamab monotherapy (Arm B)
Time frame: Up to 12 treatment cycles (Arm B) (cycle length = 21 days)
Secondary
Objective response rate (ORR) (Arms A and B)
Time frame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Duration of complete response (DOCR) (Arm A)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Up to 3 treatment cycles (cycle length = 21 days)
Duration of response (DOR) (Arm B)
Time frame: 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)
Time frame: Approximately 3 years
Serum concentration of obinutuzumab (Arms A and B)
Time frame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Serum concentration of rituximab (Arm A)
Time frame: Up to 3 treatment cycles (cycle length = 21 days)
Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)
Time frame: Up to 3 treatment cycles (cycle length = 21 days)
Eligibility criteria
Study locations (10)
Children's Hospital of Alabama
Birmingham, Alabama, 35233
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente Oakland Medical Center
Oakland, California, 94611
Kaiser Permanente - Roseville
Roseville, California, 95661
Kaiser Permanente - Santa Clara
Santa Clara, California, 95051
Johns Hopkins University
Baltimore, Maryland, 21231
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Childrens Mercy Hosp & Clinics
Kansas City, Missouri, 64108
MSKCC
New York, New York, 10065
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229