Clinical trial • Phase II • Oncology

Glofitamab for Aggressive B-cell non-Hodgkin lymphoma (relapsed/refractory) | Diffuse large B-cell lymphoma (DLBCL) (relapsed/refractory) | High-grade B-cell lymphoma (relapsed/refractory)

Phase II trial of Glofitamab for Aggressive B-cell non-Hodgkin lymphoma (relapsed/refractory) | Diffuse large B-cell lymphoma (DLBCL) (relapsed/refractory…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Aggressive B-cell non-Hodgkin lymphoma (relapsed/refractory) | Diffuse large B-cell lymphoma (DLBCL) (relapsed/refractory) | High-grade B-cell lymphoma (relapsed/refractory)
Trial Stage
Phase II
Drug Modality
Bispecific antibody | Monoclonal antibody | Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
18-11-2024
First CTIS Authorization Date
19-03-2025

Trial design

open-label Phase II trial across 14 sites in Italy, France, Germany.

Open Label
Yes
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
74

Eligibility

Recruits 74 paediatric patients.

Vulnerable Population
Vulnerable populations are selected (isVulnerablePopulationSelected = true). Subject information and informed consent forms for infants/children and pregnant partners are listed among the submitted documents (examples: 'L1_SIS and ICF infant and Privacy sheet', 'L1_SIS and ICF enfant', 'L1_SIS and ICF_PregPatient_GO45434', 'L1_SIS and ICF_PregPartner_GO45434', and country-specific ICFs). Specific consent/assent handling text and procedures are not provided in the JSON.

Inclusion criteria

  • {"criterion_text":"- Life expectancy ≥ 12 weeks"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Relapsed / refractory disease"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Participants who have failed one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant"}
  • {"criterion_text":"- 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

  • {"criterion_text":"- Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation"}
  • {"criterion_text":"- Any history of Waldenström’s macroglobulinemia"}
  • {"criterion_text":"- Primary mediastinal B-cell lymphoma"}
  • {"criterion_text":"- Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab"}
  • {"criterion_text":"- 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 endpoints

  • {"endpoint_text":"- 1. Incidence of CRS: Grade 2 or higher CRS at any time during the study, determined according to the ASTCT CRS grading criteria","definition_or_measurement_approach":"Determined according to the ASTCT CRS grading criteria"}
  • {"endpoint_text":"- 2. Incidence of CRS: Any Grade CRS, at any time during the study","definition_or_measurement_approach":"Any grade CRS occurring at any time during the study (no additional measurement approach specified beyond incidence capture)"}

Secondary endpoints

  • {"endpoint_text":"- 1. Incidence of serious CRS events, with severity determined according to the ASTCT CRS grading criteria","definition_or_measurement_approach":"Severity determined according to ASTCT CRS grading criteria"}
  • {"endpoint_text":"- 2. CRS frequency relative to the start of the infusion of each of the step-up doses of glofitamab","definition_or_measurement_approach":"Frequency measured relative to infusion start time of each step-up dose of glofitamab"}
  • {"endpoint_text":"- 3. CRS management, including outcome of patients who experienced a CRS event","definition_or_measurement_approach":"Assess management actions and outcomes in patients with CRS events (no further detail provided)"}
  • {"endpoint_text":"- 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)","definition_or_measurement_approach":"AE severity by NCI CTCAE v5.0; CRS/ICANS/HLH graded per ASTCT criteria"}
  • {"endpoint_text":"- 5. Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity","definition_or_measurement_approach":"Tolerability assessed via dose interruptions, dose reductions and dose intensity metrics"}
  • {"endpoint_text":"- 6. Study treatment discontinuation because of adverse events","definition_or_measurement_approach":"Count/record discontinuations due to AEs"}
  • {"endpoint_text":"- 7. Complete response (CR) rate","definition_or_measurement_approach":"CR rate as per study response assessment (specific response criteria not detailed in JSON)"}
  • {"endpoint_text":"- 8. Objective response rate (ORR)","definition_or_measurement_approach":"ORR as per study response assessment (specific criteria not provided)"}
  • {"endpoint_text":"- 9. Duration of response (DOR)","definition_or_measurement_approach":"DOR measured from response until progression (specific date rules not provided)"}
  • {"endpoint_text":"- 10. Duration of complete response (DOCR)","definition_or_measurement_approach":"Duration of complete response measured from CR until relapse/progression"}
  • {"endpoint_text":"- 11. Progression-free survival (PFS)","definition_or_measurement_approach":"PFS measured per study definitions (not specified in JSON)"}
  • {"endpoint_text":"- 12. Overall survival (OS)","definition_or_measurement_approach":"OS measured from date of randomization/enrollment to death (specifics not provided)"}

Recruitment

Registry Or Advocacy Recruitment
True, Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi (listed as patient organisation/association)
Planned Sample Size
74
Recruitment Window Months
48
Consent Approach
Subject information and informed consent forms are submitted and include versions for main subjects, infant/child, pregnant patient and pregnant partner (documents include e.g., 'L1_SIS and ICF Main_GO45434_redacted', 'L1_SIS and ICF infant and Privacy sheet', 'L1_SIS and ICF_PregPatient_GO45434', 'L1_SIS and ICF_PregPartner_GO45434'). Country-specific documents are present for member states (France, Italy, Germany) and protocol translations exist (English, French, German, Italian). Specific procedural text on who provides consent/assent and language availability beyond the document listings is not provided in the JSON.

Geography

Total Number Of Sites
14
Total Number Of Participants
26

Italy

Earliest CTIS Part Ii Submission Date
25-07-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
626
Number Of Sites
5
Number Of Participants
6

Sites

Site Name
Humanitas Mirasole S.p.A.
Department Name
U.O. di Oncologia Medica ed Ematologia
Contact Person Name
Carmelo Carlo-Stella
Contact Person Email
carmelo.carlostella@hunimed.eu
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Divisione di Oncoematologia
Contact Person Name
Enrico Derenzini
Contact Person Email
Enrico.Derenzini@ieo.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
U.O. Ematologia
Contact Person Name
Alessandra Tucci
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
S.C. Ematologia Oncologica
Contact Person Name
Antonio Pinto
Contact Person Email
a.pinto@istitutotumori.na.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Ematologia
Contact Person Name
Gerardo Musuraca
Contact Person Email
gerardo.musuraca@irst.emr.it

France

Earliest CTIS Part Ii Submission Date
20-12-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
484
Number Of Sites
5
Number Of Participants
9

Sites

Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Hematology
Contact Person Name
Charles Herbaux
Contact Person Email
c-herbaux@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Hematology
Contact Person Name
Roch Houot
Contact Person Email
Roch.HOUOT@chu-rennes.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Hematology
Contact Person Name
François-Xavier Gros
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Hematology
Contact Person Name
Lucile Bussot
Contact Person Email
lbussot@chu-grenoble.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Hematology
Contact Person Name
Emmanuel GYAN
Contact Person Email
e.gyan@chu-tours.fr

Germany

Earliest CTIS Part Ii Submission Date
17-02-2025
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
420
Number Of Sites
4
Number Of Participants
11

Sites

Site Name
Universitaetsklinikum Magdeburg AöR
Department Name
Hämatology
Contact Person Name
Vanja Zeremski
Contact Person Email
vanja.zeremski@med.ovgu.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Hämatologie
Contact Person Name
Björn Chapuy
Contact Person Email
bjoern.chapuy@charite.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Hämatologie
Contact Person Name
Björn Chapuy
Contact Person Email
bjoern.chapuy@charite.de
Site Name
University Hospital Cologne AöR
Department Name
Hämatology
Contact Person Name
Peter Borchmann
Contact Person Email
peter.borchmann@uk-koeln.de

Sponsor

Primary sponsor

Full Name
F. Hoffmann-La Roche AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Third parties

  • {"country":"United States","full_name":"FACIT.Org Inc.","duties_or_roles":"Clinical Outcome Assessment (eCOA, ePRO) Provider","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient Reimbursement Provider","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Belgium","full_name":"Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi","duties_or_roles":"Clinical Outcome","organisation_type":"Patient organisation/association"}
  • {"country":"France","full_name":"Median Technologies","duties_or_roles":"Imaging","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"IxRS Provider","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central Laboratory Provider","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Glofitamab
Active Substance
Glofitamab
Modality
Bispecific antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation available (marketingAuthNumber EU/1/23/1742/002)
Investigational Product Name
Gemcitabine
Active Substance
Gemcitabine
Modality
Small molecule
Authorisation Status
Marketing authorisation available (marketingAuthNumber HR-H-808889278 / other MA numbers listed)
Investigational Product Name
Oxaliplatin
Active Substance
Oxaliplatin
Modality
Small molecule
Authorisation Status
Marketing authorisation available (multiple marketing author numbers listed)
Investigational Product Name
Obinutuzumab
Active Substance
Obinutuzumab
Modality
Monoclonal antibody
Authorisation Status
Marketing authorisation available (marketingAuthNumber EU/1/14/937/001)
Combination Treatment
Yes

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