iMATRIX GLO: A Study to Evaluate Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05533775

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

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
Mature B-Cell Non-Hodgkin Lymphoma	Drug: Obinutuzumab Drug: Glofitamab Drug: Rituximab Drug: Ifosfamide Drug: Carboplatin Drug: Etoposide Drug: Tocilizumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

65 participants

Allocation:

N/A

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Anticipated Study Start Date :

Oct 15, 2022

Anticipated Primary Completion Date :

Oct 15, 2027

Anticipated Study Completion Date :

Oct 15, 2027

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

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

Ages Eligible for Study:

6 Months to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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