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

Mature B-Cell Non-Hodgkin Lymphoma Clinical Trial

— iMATRIX GLO  

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 Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05533775
• Other study ID #: CO43810
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 16, 2022
• Est. completion date: October 15, 2027

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CO43810 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: October 15, 2027
• Est. primary completion date: October 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Mature B-Cell Non-Hodgkin Lymphoma

Intervention

Drug:
• Obinutuzumab
Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)
• Glofitamab
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)
• Rituximab
Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)
• Ifosfamide
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)
• Carboplatin
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)
• Etoposide
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)
• Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events

Locations

Country	Name	City	State
Australia	Perth Children's Hospital	Nedlands	Western Australia
Australia	Queensland Children?s Hospital	South Brisbane	Queensland
Denmark	Rigshospitalet; Ny Medicin til Børn med Kræft	København Ø
France	Hôpital Pellegrin; Service d'oncologie pédiatrique	Bordeaux
France	Gustave Roussy	Villejuif
Germany	Universitaetsklinikum Muenster; Paedriatrische Haematologie und Onkologie	Muenster
Italy	IRCCS Ospedale Pediatrico Bambino Gesù; Clinical trial center - Pad. Salviati 1 floor	Roma	Lazio
Italy	Ospedaliera Ospedale Infantile Regina Margherita; Oncoematologia Pediatrica-Centro Trapianti Cellule	Torino	Piemonte
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital- Pediatric Site	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Infantil Universitario Niño Jesus; Servicio de Onco-hematologia	Madrid
United States	Johns Hopkins University	Baltimore	Maryland
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Childrens Mercy Hosp & Clinics	Kansas City	Missouri
United States	MSKCC	New York	New York
United States	Kaiser Permanente Oakland Medical Center	Oakland	California
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	Kaiser Permanente - Roseville	Roseville	California
United States	Kaiser Permanente - Santa Clara	Santa Clara	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  France,  Germany,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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)		Up to 3 treatment cycles (cycle length = 21 days)
Primary	Percentage of participants with adverse events (AEs) (Arm A)		Approximately 3 years
Primary	Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)		Up to 3 treatment cycles (cycle length = 21 days)
Primary	Serum concentration of glofitamab monotherapy (Arm B)		Up to 12 treatment cycles (Arm B) (cycle length = 21 days)
Secondary	Objective response rate (ORR) (Arms A and B)		Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Percentage of participants with AEs (arm B)		Approximately 3 years
Secondary	Serum concentration of obinutuzumab (Arms A and B)		Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Secondary	Serum concentration of rituximab (Arm A)		Up to 3 treatment cycles (cycle length = 21 days)
Secondary	Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)		Up to 3 treatment cycles (cycle length = 21 days)