Clinical trial • Phase I/II • Oncology
TOCILIZUMAB for Relapsed/Refractory B-cell Non-Hodgkin lymphoma
Phase I/II trial of TOCILIZUMAB for Relapsed/Refractory B-cell Non-Hodgkin lymphoma.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Relapsed/Refractory B-cell Non-Hodgkin lymphoma
- Trial Stage
- Phase I/II
- Drug Modality
- Monoclonal antibody|Bispecific antibody
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 11-01-2024
- First CTIS Authorization Date
- 27-02-2024
Trial design
open-label, glofitamab monotherapy (used as comparator in part iii); obinutuzumab single fixed dose 1 g iv pre-treatment administered seven days ±1 day prior to first administration (and administered concomitantly at subsequent cycles at least 1 hour apart) (used as pre-treatment across parts)-controlled, adaptive Phase I/II trial in France, Belgium, Denmark and others.
- Open Label
- Yes
- Comparator
- Glofitamab monotherapy (used as comparator in Part III); Obinutuzumab single fixed dose 1 g IV pre-treatment administered seven days ±1 day prior to first administration (and administered concomitantly at subsequent cycles at least 1 hour apart) (used as pre-treatment across parts)
- Adaptive
- True, dose-escalation design in Part I to determine maximum tolerated dose and/or recommended Phase 2 dose (RP2D); dose-escalation and dose-finding adaptive elements
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 157
Eligibility
Recruits 157 adults.
Inclusion criteria
- {"criterion_text":"- Willing and able to comply with protocol-mandated hospitalization per protocol. Participants must also be willing to comply with all study-related procedures\n- A history or status of: - a histologically-confirmed hematological malignancy that is expected to express CD19 and CD20; - certain B-cell malignancies with relapse after or failure to respond to at least one prior treatment regimen for Part I and II - certain B-cell malignancies with relapse after or failure to respond to only one prior systemic treatment regimen for Part 3 - no available treatment options that are expected to prolong survival\n- Must have at least one measureable target lesion (>= 1.5 cm) in its largest dimension by computed tomography scan\n- Able and willing to provide a fresh biopsy from a safely accessible site, per Investigator’s determination, providing the participant has more than one measurable target lesion. However, in the absence of fresh biopsy, provide the most recent archival tumor tissue samples that are preferably not older than 6 months and preferably not confounded by major events. For archival biopsies formalin-fixed, paraffin-embedded blocks are preferred, but if not available, unstained slides are acceptable\n- Eastern Cooperative Oncology Group performance status of 0 or 1\n- Life expectancy of >= 12 weeks"}
Exclusion criteria
- {"criterion_text":"- Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count or the presence of abnormal cells in the peripheral blood signifying circulating lymphoma cells\n- Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture\n- Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics\n- Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines or monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on D-7\n- History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease - Grade >= 3 AEs with the exception of Grade 3 endocrinopathy managed with replacement therapy and Grade 3 CRS which has fully resolved - Grade 1-2 AEs that did not resolve to baseline after treatment discontinuation\n- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational or approved anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to obinutuzumab infusion"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part I/II 1. Nature and frequency of dose-limiting toxicities (DLTs)\n- Part I/II 2. Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and for CRS the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading\n- Part III 3. Investigator assessed CR rate as assessed by FDG-PET/CT scan","definition_or_measurement_approach":"Part I/II 1: DLTs assessed during dose-escalation period per protocol definitions; Part I/II 2: AEs graded per NCI CTCAE v5.0; CRS graded per ASTCT consensus grading; Part III 3: Complete response (CR) rate assessed by investigator using FDG-PET/CT scan"}
Secondary endpoints
- {"endpoint_text":"- Part I/II 1. Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab\n- Part I/II 2. Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab\n- Part I/II 3. Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab\n- Part I/II 4. Clearance (CL), Volume of distribution of steady state (Vss) and half-life (t½) if data permit\n- Part I/II 5. Analysis of dose-linearity in exposure\n- Part I/II 6. Additional PK parameters may be determined as appropriate\n- Part I/II 7. Incidence and titer of englumafusp alfa anti-drug antibodies (ADAs) during the study relative to prevalence of ADAs at baseline\n- Part I/II 8. Overall response rate (ORR)\n- Part I/II 9. Disease control rate (DCR)\n- Part III 10. Incidence, nature, and severity of AEs graded according to the NCI CTCAE v5.0 and for CRS the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading\n- Part III 11. Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab\n- Part III 12. Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab\n- Part III 13. Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab\n- Part III 14. Clearance (CL), Volume of distribution of steady state (Vss) and half-life (t½) if data permit of englumafusp alfa in combination with glofitamab\n- Part III 15. Analysis of dose-linearity in exposure\n- Part III 16. Additional PK parameters may be determined as appropriate\n- Part III 17. Incidence and titer of englumafusp alfa anti-drug antibodies (ADAs) during the study relative to prevalence of ADAs at baseline\n- Part III 18. Overall response rate (ORR)\n- Part III 19. Duration of complete response (DOCR)\n- Part III 20. Progression-free survival (PFS)\n- Part III 21. Overall survival (OS)\n- Part III 22.Time to first complete response (TFCR)\n- Part III 23. Time to first overall response (TFOR)\n- Part III 24 Change from baseline in physical function, role function, and HRQoL based on EORTC QLQ C30\n- Part III 25. Change from baseline in disease-related symptoms based on the FACT-Lym Lymphoma scale\n- Part III 26. Baseline levels and change from baseline of cellular biomarkers in blood and tumor tissue, using markers of B, and T-cell lineage\n- Part I/II 27. Baseline levels and change from baseline of cellular biomarkers in blood, using markers of B-, T- and NK-cell lineage","definition_or_measurement_approach":"PK endpoints: AUC, Cmax, Cmin, CL, Vss, t½ measured from serum PK sampling; ADA incidence and titer measured by immunogenicity assays; efficacy endpoints (ORR, DOCR, PFS, OS, TFCR, TFOR) assessed per protocol (imaging/clinical criteria); PROs via EORTC QLQ-C30 and FACT-Lym; cellular biomarkers measured in blood and tumor tissue using lineage markers"}
Recruitment
- Planned Sample Size
- 157
- Recruitment Window Months
- 88
- Consent Approach
- Informed consent obtained using Subject Information Sheet and Informed Consent Form (L1_SIS and ICF) materials. ICF/SIS documents available in multiple language versions (titles indicate English, French, Spanish, Italian, Dutch/BE-NL). Specific assent/consent procedural details not provided in the JSON.
Geography
- Total Number Of Sites
- 18
- Total Number Of Participants
- 194
France
- Earliest CTIS Part Ii Submission Date
- 29-01-2024
- Latest Decision Or Authorization Date
- 22-03-2024
- Processing Time Days
- 53
- Number Of Sites
- 4
- Number Of Participants
- 50
Sites
- Site Name
- Hospices Civils De Lyon
- Department Name
- Service hématologie clinique
- Contact Person Name
- Hervé Ghesquieres
- Contact Person Email
- herve.ghesquieres@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Service hématologie clinique
- Contact Person Name
- Roch Houot
- Contact Person Email
- roch.houot@chu-rennes.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Service des maladies du sang
- Contact Person Name
- FRANCK MORSCHHAUSER
- Contact Person Email
- franck.morschhauser@chru-lille.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Service hématologie clinique
- Contact Person Name
- Guillaume Cartron
- Contact Person Email
- g-cartron@chu-montpellier.fr
Belgium
- Earliest CTIS Part Ii Submission Date
- 29-01-2024
- Latest Decision Or Authorization Date
- 28-02-2024
- Processing Time Days
- 30
- Number Of Sites
- 1
- Number Of Participants
- 15
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Hematology
- Contact Person Name
- Fritz Offner
- Contact Person Email
- fritz.offner@uzgent.be
Denmark
- Earliest CTIS Part Ii Submission Date
- 29-01-2024
- Latest Decision Or Authorization Date
- 27-02-2024
- Processing Time Days
- 29
- Number Of Sites
- 3
- Number Of Participants
- 40
Sites
- Site Name
- Rigshospitalet
- Department Name
- Rigshospitalet; Fase 1 Enhed - Onkologi
- Contact Person Name
- Martin Hutchings
- Contact Person Email
- Martin.hutchings@regionh.dk
- Site Name
- Odense University Hospital
- Department Name
- Hæmatologisk Afdeling
- Contact Person Name
- Peter Brændstrup
- Contact Person Email
- Peter.Braendstrup@rsyd.dk
- Site Name
- Aarhus Universitetshospital
- Department Name
- Blodsygdomme
- Contact Person Name
- Judit Jørgensen
- Contact Person Email
- judijoer@rm.dk
Spain
- Earliest CTIS Part Ii Submission Date
- 29-01-2024
- Latest Decision Or Authorization Date
- 27-02-2024
- Processing Time Days
- 29
- Number Of Sites
- 6
- Number Of Participants
- 29
Sites
- Site Name
- Clinica Universidad De Navarra (Pamplona)
- Department Name
- Hematology
- Contact Person Name
- Miguel Ángel Canales
- Contact Person Email
- macanales@unav.es
- Site Name
- Hospital Universitario Virgen De La Victoria
- Department Name
- Hematology
- Contact Person Name
- Antonio Rueda
- Contact Person Email
- antonio.rueda.dominguez.sspa@juntadeandalucia.es
- Site Name
- Clinica Universidad De Navarra (Madrid)
- Department Name
- Hematology
- Contact Person Name
- Miguel Ángel Canales
- Contact Person Email
- macanales@unav.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Hematology
- Contact Person Name
- Francesc Bosh
- Contact Person Email
- fboschct@vhio.net
- Site Name
- Institut Catala D'oncologia
- Department Name
- Hematology
- Contact Person Name
- Anna Sureda
- Contact Person Email
- asureda@iconcologia.net
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Hematology
- Contact Person Name
- Tycho Baumasnn
- Contact Person Email
- tycho.baumann@gmail.com
Italy
- Earliest CTIS Part Ii Submission Date
- 29-01-2024
- Latest Decision Or Authorization Date
- 26-03-2024
- Processing Time Days
- 57
- Number Of Sites
- 4
- Number Of Participants
- 60
Sites
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- SC Ematologia e Oncologia
- Contact Person Name
- Antonello Pinto
- Contact Person Email
- a.pinto@istitutotumori.na.it
- Site Name
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
- Department Name
- UOC Ematologia
- Contact Person Name
- Giuseppe Gritti
- Contact Person Email
- g.gritti@asst-pg23.it
- Site Name
- Istituto Europeo Di Oncologia S.r.l.
- Department Name
- Clinical Haemato-Oncology
- Contact Person Name
- Enrico Derenzini
- Contact Person Email
- Enrico.Derenzini@ieo.it
- Site Name
- Humanitas Research Hospital
- Department Name
- Dipartimento Oncologia e Ematologia
- Contact Person Name
- Carmelo Carlo-Stella
- Contact Person Email
- carmelo.carlostella@hunimed.eu
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Q Squared Solutions Limited
- Responsibilities
- Not specified (sponsorDuties code 4)
- Name
- Q Squared Solutions LLC
- Responsibilities
- Not specified (sponsorDuties code 4)
- Name
- Iqvia Rds Inc.
- Responsibilities
- ECG Services
- Name
- PPD Development LP
- Responsibilities
- Not specified (sponsorDuties code 4)
- Name
- Endpoint Clinical Inc.
- Responsibilities
- sponsorDuties code 14
Third parties
- {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"sponsorDuties codes: [ {\"id\":980209,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: [ {\"id\":980208,\"code\":\"4\"} ]","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"sponsorDuties codes: [ {\"id\":980210,\"code\":\"4\"} ]","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"ECG Services","organisation_type":"Pharmaceutical company"}
- {"country":"China","full_name":"Frontage Laboratories (Shanghai) Co. Ltd.","duties_or_roles":"sponsorDuties codes: [ {\"id\":980213,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"China","full_name":"Sequanta Technologies Co. Ltd.","duties_or_roles":"sponsorDuties codes: [ {\"id\":980212,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Other Third Party Duty","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties codes: [ {\"id\":980217,\"code\":\"14\"} ]","organisation_type":"Pharmaceutical company"}
- {"country":"China","full_name":"Q Squared Solutions (Beijing) Co. Ltd.","duties_or_roles":"sponsorDuties codes: [ {\"id\":980207,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"MicroCoat Biotechnologie GmbH","duties_or_roles":"sponsorDuties codes: [ {\"id\":980214,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"sponsorDuties codes: [ {\"id\":980216,\"code\":\"4\"} ]","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: [ {\"id\":980211,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- RoActemra 20 mg/mL concentrate for solution for infusion
- Active Substance
- TOCILIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- IV INFUSION
- Route
- IV INFUSION
- Authorisation Status
- Authorised (marketing authorization referenced PRD2154622, prodAuthStatus 2)
- Investigational Product Name
- CD19 4-1 BBL (RO7227166 / Englumafusp Alfa)
- Active Substance
- ENGLUMAFUSP ALFA
- Modality
- Bispecific antibody
- Routes Of Administration
- IV INFUSION
- Route
- IV INFUSION
- Authorisation Status
- Not authorised (prodAuthStatus 1 indicates no marketing authorisation in productDictionaryInfo)
- Investigational Product Name
- Gazyvaro 1,000 mg concentrate for solution for infusion
- Active Substance
- OBINUTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- IV INFUSION
- Route
- IV INFUSION
- Authorisation Status
- Authorised (marketing authorization referenced PRD1753415, prodAuthStatus 2)
- Orphan Designation
- Yes
- Investigational Product Name
- Columvi 10 mg concentrate for solution for infusion
- Active Substance
- GLOFITAMAB
- Modality
- Bispecific antibody
- Routes Of Administration
- IV INFUSION
- Route
- IV INFUSION
- Authorisation Status
- Authorised (marketing authorization referenced PRD10561232, prodAuthStatus 2)
- Combination Treatment
- Yes
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