iMATRIX GLO: A Study to Evaluate Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days). |
Drug: Obinutuzumab
Participants will receive intravenous (IV) obinutuzumab pretreatment during Cycle 1 (cycle length = 21 days)
Drug: Glofitamab
Participants will receive IV glofitamab for up to 3 cycles (Arm A) or 12 cycles (Arm B) (cycle length = 21 days)
Drug: Rituximab
Participants will receive IV rituximab on Day 5 of Cycles 2 and 3 (cycle length = 21 days)
Drug: Ifosfamide
Participants will receive ifosfamide for up to 3 cycles (cycle length = 21 days)
Drug: Carboplatin
Participants will receive IV carboplatin during Cycles 1-3 (cycle length = 21 days)
Drug: Etoposide
Participants will receive IV etoposide during Cycles 1-3 (cycle length = 21 days)
Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events
|
Experimental: Arm B Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days). |
Drug: Obinutuzumab
Participants will receive intravenous (IV) obinutuzumab pretreatment during Cycle 1 (cycle length = 21 days)
Drug: Glofitamab
Participants will receive IV glofitamab for up to 3 cycles (Arm A) or 12 cycles (Arm B) (cycle length = 21 days)
Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events
|
Outcome Measures
Primary Outcome Measures
- 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 14 months]
- 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
- 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 14 months)]
- Progression-free survival (PFS) (Arm A) [From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 14 months)]
- 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 14 months)]
- Overall survival (OS) (Arms A and B) [From the first study treatment to the date of death from any cause (Arm A = approximately 14 months, Arm B = approximately 20 months)]
- 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 20 months)]
- Percentage of participants with AEs (arm B) [Approximately 20 months]
- 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)]
Eligibility Criteria
Criteria
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 prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC), 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 following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens 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), or human immunodeficiency virus (HIV)
-
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
-
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-LaRoche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CO43810