Trial Title:
A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
NCT ID:
NCT05533775
Condition:
Mature B-Cell Non-Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Rituximab
Obinutuzumab
Carboplatin
Etoposide
Ifosfamide
Conditions: Keywords:
Relapsed
Refractory
Pediatrics
B-NHL
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of
Cycle 1 (Cycle length = 21 days)
Arm group label:
Arm A
Arm group label:
Arm B
Intervention type:
Drug
Intervention name:
Glofitamab
Description:
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)
Arm group label:
Arm A
Arm group label:
Arm B
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle
length = 21 days)
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Ifosfamide
Description:
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)
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
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)
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Etoposide
Description:
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)
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Tocilizumab
Description:
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome
(CRS) events
Arm group label:
Arm A
Arm group label:
Arm B
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).
Criteria for 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
Gender:
All
Minimum age:
6 Months
Maximum age:
30 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital of Alabama
Address:
City:
Birmingham
Zip:
35233
Country:
United States
Status:
Recruiting
Facility:
Name:
UCSF Benioff Children's Hospital Oakland
Address:
City:
Oakland
Zip:
94609
Country:
United States
Status:
Recruiting
Facility:
Name:
Kaiser Permanente Oakland Medical Center
Address:
City:
Oakland
Zip:
94611
Country:
United States
Status:
Recruiting
Facility:
Name:
Kaiser Permanente - Roseville
Address:
City:
Roseville
Zip:
95661
Country:
United States
Status:
Recruiting
Facility:
Name:
Kaiser Permanente - Santa Clara
Address:
City:
Santa Clara
Zip:
95051
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Johns Hopkins University
Address:
City:
Baltimore
Zip:
21205
Country:
United States
Status:
Recruiting
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Facility:
Name:
Childrens Mercy Hosp & Clinics
Address:
City:
Kansas City
Zip:
64108
Country:
United States
Status:
Recruiting
Facility:
Name:
MSKCC
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Facility:
Name:
Cincinnati Children's Hospital Medical Center
Address:
City:
Cincinnati
Zip:
45229
Country:
United States
Status:
Recruiting
Facility:
Name:
Queensland Children?s Hospital
Address:
City:
South Brisbane
Zip:
4101
Country:
Australia
Status:
Recruiting
Facility:
Name:
Perth Children's Hospital
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Facility:
Name:
Rigshospitalet; Ny Medicin til Børn med Kræft
Address:
City:
København Ø
Zip:
2100
Country:
Denmark
Status:
Recruiting
Facility:
Name:
Hôpital Pellegrin; Service d'oncologie pédiatrique
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Muenster; Paedriatrische Haematologie und Onkologie
Address:
City:
Muenster
Zip:
48149
Country:
Germany
Status:
Recruiting
Facility:
Name:
IRCCS Ospedale Pediatrico Bambino Gesù; Clinical trial center - Pad. Salviati 1 floor
Address:
City:
Roma
Zip:
00165
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ospedaliera Ospedale Infantile Regina Margherita; Oncoematologia Pediatrica-Centro Trapianti Cellule
Address:
City:
Torino
Zip:
10126
Country:
Italy
Status:
Recruiting
Facility:
Name:
Seoul National University Hospital- Pediatric Site
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Infantil Universitario Niño Jesus; Servicio de Onco-hematologia
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Status:
Recruiting
Start date:
November 16, 2022
Completion date:
October 15, 2027
Lead sponsor:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Hoffmann-La Roche
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05533775
