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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05533775




Registration number
NCT05533775
Ethics application status
Date submitted
6/09/2022
Date registered
9/09/2022

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
CO43810
Universal Trial Number (UTN)
Trial acronym
iMATRIX GLO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mature B-Cell Non-Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Glofitamab
Treatment: Drugs - Rituximab
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Tocilizumab

Experimental: Arm A - Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).

Experimental: Arm B - Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).


Treatment: Drugs: Obinutuzumab
Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)

Treatment: Drugs: 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)

Treatment: Drugs: Rituximab
Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

Treatment: Drugs: 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)

Treatment: Drugs: 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)

Treatment: Drugs: 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)

Treatment: Drugs: Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to 3 treatment cycles (cycle length = 21 days)
Primary outcome [2] 0 0
Percentage of participants with adverse events (AEs) (Arm A)
Timepoint [2] 0 0
Approximately 3 years
Primary outcome [3] 0 0
Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)
Timepoint [3] 0 0
Up to 3 treatment cycles (cycle length = 21 days)
Primary outcome [4] 0 0
Serum concentration of glofitamab monotherapy (Arm B)
Timepoint [4] 0 0
Up to 12 treatment cycles (Arm B) (cycle length = 21 days)
Secondary outcome [1] 0 0
Objective response rate (ORR) (Arms A and B)
Timepoint [1] 0 0
Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Secondary outcome [2] 0 0
Duration of complete response (DOCR) (Arm A)
Timepoint [2] 0 0
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 outcome [3] 0 0
Progression-free survival (PFS) (Arm A)
Timepoint [3] 0 0
From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 3 years)
Secondary outcome [4] 0 0
Event-free survival (EFS) (Arm A)
Timepoint [4] 0 0
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 outcome [5] 0 0
Overall survival (OS) (Arms A and B)
Timepoint [5] 0 0
From the first study treatment to the date of death from any cause (Arm A = approximately 3 years, Arm B = approximately 4 years)
Secondary outcome [6] 0 0
Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A)
Timepoint [6] 0 0
Up to 3 treatment cycles (cycle length = 21 days)
Secondary outcome [7] 0 0
Duration of response (DOR) (Arm B)
Timepoint [7] 0 0
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 outcome [8] 0 0
Percentage of participants with AEs (arm B)
Timepoint [8] 0 0
Approximately 3 years
Secondary outcome [9] 0 0
Serum concentration of obinutuzumab (Arms A and B)
Timepoint [9] 0 0
Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Secondary outcome [10] 0 0
Serum concentration of rituximab (Arm A)
Timepoint [10] 0 0
Up to 3 treatment cycles (cycle length = 21 days)
Secondary outcome [11] 0 0
Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)
Timepoint [11] 0 0
Up to 3 treatment cycles (cycle length = 21 days)

Eligibility
Key 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
Minimum age
6 Months
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/10/2027
Actual
Sample size
Target
65
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Queensland Children?s Hospital - South Brisbane
Recruitment hospital [2] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
Denmark
State/province [8] 0 0
København Ø
Country [9] 0 0
France
State/province [9] 0 0
Bordeaux
Country [10] 0 0
France
State/province [10] 0 0
Villejuif
Country [11] 0 0
Germany
State/province [11] 0 0
Muenster
Country [12] 0 0
Italy
State/province [12] 0 0
Lazio
Country [13] 0 0
Italy
State/province [13] 0 0
Piemonte
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-LaRoche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: CO43810 https://forpatients.roche.com
Address 0 0
Country 0 0
Phone 0 0
888-662-6728
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05533775