Clinical trial NCT05533775: A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Mature B-Cell Non-Hodgkin Lymphoma
Keywords: Relapsed
Refractory
Pediatrics
B-NHL
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-09-09
Enrollment: 65
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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, 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

Primary outcomes:
measure: 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)
timeFrame: Up to 3 treatment cycles (cycle length = 21 days)
measure: Percentage of participants with adverse events (AEs) (Arm A)
timeFrame: Approximately 3 years
measure: Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)
timeFrame: Up to 3 treatment cycles (cycle length = 21 days)
measure: Serum concentration of glofitamab monotherapy (Arm B)
timeFrame: Up to 12 treatment cycles (Arm B) (cycle length = 21 days)
Secondary outcomes:
measure: Objective response rate (ORR) (Arms A and B)
timeFrame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
measure: Duration of complete response (DOCR) (Arm A)
timeFrame: 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)
measure: Progression-free survival (PFS) (Arm A)
timeFrame: From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 3 years)
measure: Event-free survival (EFS) (Arm A)
timeFrame: 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)
measure: Overall survival (OS) (Arms A and B)
timeFrame: From the first study treatment to the date of death from any cause (Arm A = approximately 3 years, Arm B = approximately 4 years)
measure: Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A)
timeFrame: Up to 3 treatment cycles (cycle length = 21 days)
measure: Duration of response (DOR) (Arm B)
timeFrame: 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)
measure: Percentage of participants with AEs (arm B)
timeFrame: Approximately 3 years
measure: Serum concentration of obinutuzumab (Arms A and B)
timeFrame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
measure: Serum concentration of rituximab (Arm A)
timeFrame: Up to 3 treatment cycles (cycle length = 21 days)
measure: Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)
timeFrame: Up to 3 treatment cycles (cycle length = 21 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland Medical Center
state: California
city: Roseville
country: United States
facility: Kaiser Permanente - Roseville
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente - Santa Clara
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Kansas City
country: United States
facility: Childrens Mercy Hosp & Clinics
state: Missouri
city: New York
country: United States
facility: MSKCC
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: South Brisbane
country: Australia
facility: Queensland Children?s Hospital
state: Queensland
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Sao Paulo
country: Brazil
facility: Graacc-Grupo de Apoio ao adolescente e a crianca com cancer
state: São Paulo
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
state: Lazio
city: Torino
country: Italy
facility: Ospedaliera Ospedale Infantile Regina Margherita
state: Piemonte
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital- Pediatric Site
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesus
Study officials:
affiliation: Hoffmann-LaRoche
name: Clinical Trials
role: STUDY_DIRECTOR
References: