A Study to Understand the Optimization of the Cytokine Release Syndrome Profile for Glofitamab along with Gemcitabine Plus Oxaliplatin in Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin’s Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Apr 2025 → ongoing

Decision date (initial)

2025-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the frequency of cytokine release syndrome (CRS)

Secondary objectives 3

1. To evaluate the frequency and severity of CRS
2. To evaluate the safety of glofitamab-gemcitabine and oxaliplatin (Glofit-GemOx)
3. To evaluate the efficacy of Glofit-GemOx

Conditions and MedDRA coding

Relapsed/Refractory Aggressive B-Cell Non-Hodgkin’s Lymphoma (NHL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Life expectancy ≥ 12 weeks
2. Participant with histologically confirmed diffuse large B-cell lymphoma, (de novo or transformed from a follicular lymphoma) with one of the following diagnoses according to World Health Organization, fifth edition (Alaggio et al. 2022):-DLBCL not otherwise specified (NOS) - High-Grade B-Cell Lymphoma (HGBL), NOS; – DLBCL/HGBL with myelocytomatosis proto-oncogene (MYC) and B-cell lymphoma 2 (BCL2) rearrangements
3. Relapsed / refractory disease
4. At least one prior line of systemic therapy - Participants may have undergone ASCT prior to recruitment - Local therapies (e.g., radiotherapy) will not be considered as lines of therapy
5. Participants who have failed one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant
6. At least one bi-dimensionally measurable ( > 1.5 cm) nodal lesion, or one bi-dimensionally measurable ( > 1 cm) extranodal lesion, as measured on CT scan

Exclusion criteria 5

1. Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
2. Any history of Waldenström’s macroglobulinemia
3. Primary mediastinal B-cell lymphoma
4. Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab
5. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Incidence of CRS: Grade 2 or higher CRS at any time during the study, determined according to the ASTCT CRS grading criteria
2. 2. Incidence of CRS: Any Grade CRS, at any time during the study

Secondary endpoints 12

1. 1. Incidence of serious CRS events, with severity determined according to the ASTCT CRS grading criteria
2. 2. CRS frequency relative to the start of the infusion of each of the step-up doses of glofitamab
3. 3. CRS management, including outcome of patients who experienced a CRS event
4. 4. Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0 , except CRS, ICANS, and HLH that will be graded using ASTCT grading criteria (Lee et al. 2019; Hines et al. 2023)
5. 5. Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity
6. 6. Study treatment discontinuation because of adverse events
7. 7. Complete response (CR) rate
8. 8. Objective response rate (ORR)
9. 9. Duration of response (DOR)
10. 10. Duration of complete response (DOCR)
11. 11. Progression-free survival (PFS)
12. 12. Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 6

Locations

3 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications