Clinical trial • Phase I/II • Oncology|Psychiatry
GLOFITAMAB for Relapsed/refractory B-cell non-Hodgkin lymphoma | Diffuse large B-cell lymphoma | Follicular lymphoma | Mantle cell lymphoma
Phase I/II trial of GLOFITAMAB for Relapsed/refractory B-cell non-Hodgkin lymphoma | Diffuse large B-cell lymphoma | Follicular lymphoma | Mantle cell lym…
Overview
- Trial Therapeutic Area
- Oncology|Psychiatry
- Trial Disease
- Relapsed/refractory B-cell non-Hodgkin lymphoma | Diffuse large B-cell lymphoma | Follicular lymphoma | Mantle cell lymphoma
- Trial Stage
- Phase I/II
- Drug Modality
- Bispecific antibody|Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 09-07-2024
- First CTIS Authorization Date
- 01-08-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase I/II trial in Belgium, Poland, Denmark and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, dose-escalation design with single-patient cohorts in Part I (intra-patient escalation allowed), multiple-patient cohorts in Part II to determine MTD/OBD and DLT profile; Part II starts when a flat dose of 810 µg is reached or a glofitamab-related Grade 2 AE (or DLT) is observed during a Part I patient’s 4-week DLT window. DLT assessment period is 4 weeks (28 days).
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 560
Eligibility
Recruits 560 Vulnerable population selected (populationOfTrialSubjects.isVulnerablePopulationSelected = true). Subject information and informed consent forms and an 'Informed consent form procedure' document are listed (multiple language versions available)..
- Pregnancy Exclusion
- Pregnant, breast-feeding or intending to become pregnant during the study
- Vulnerable Population
- Vulnerable population selected (populationOfTrialSubjects.isVulnerablePopulationSelected = true). Subject information and informed consent forms and an 'Informed consent form procedure' document are listed (multiple language versions available).
Inclusion criteria
- {"criterion_text":"- Patient willing and able to comply with protocol-mandated hospitalizations upon administration of glofitamab and also all study-related procedures, in Part III, this includes completion of Patient-reported outcome"}
- {"criterion_text":"- For Parts I and II:Grades 1-3b FL; Marginal zone lymphoma; Mantle cell lymphoma; DLBCL; Primary mediastinal B-cell lymphoma; Richter’s transformation; and transformed FL (trFL) For Part III expansion cohorts: DLBCL cohort (r/r DLBCL, not otherwise specified [NOS]/high-grade B-cell lymphoma [HGBCL],PMBCL and trFL). Patients must have relapsed after or failed to respond to at least two prior systemic treatment regimens (including at least one prior regimen containing anthracycline, and at least one containing an anti CD20-directed therapy). cohort: R/R FL cohort: Grades 1-3a FL patients must have relapsed after or failed to respond to at least two prior lines of systemic therapy and must have received prior treatment with rituximab and alkylating agents"}
- {"criterion_text":"- For Part III expansion cohorts: Life expectancy (in the opinion of the Investigator) of >= 12 weeks"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- Eastern Cooperative Oncology Group performance status of 0 or 1"}
- {"criterion_text":"- Adequate liver, hematological, and renal function"}
Exclusion criteria
- {"criterion_text":"- Inability to comply with protocol mandated hospitalization and restrictions"}
- {"criterion_text":"- Patients with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma"}
- {"criterion_text":"- Patients with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)"}
- {"criterion_text":"- Patients with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to Gpt infusion or by clinical judgment in the absence of a positive blood culture"}
- {"criterion_text":"- Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing"}
- {"criterion_text":"- Pregnant, breast-feeding or intending to become pregnant during the study"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Incidence of dose-limiting toxicity (DLTs)","definition_or_measurement_approach":"DLTs assessed during the DLT assessment period (4 weeks/28 days) as defined by the protocol"}
- {"endpoint_text":"- 2. The primary safety endpoints will be incidence of all adverse events, changes in vital signs, clinical laboratory values, electrocardiograms and incidence of DLTs","definition_or_measurement_approach":"Incidence assessed by AE reporting, vital signs monitoring, clinical lab tests, ECGs and DLT assessment per protocol"}
- {"endpoint_text":"- 3. Incidence, nature, and severity of all adverse events","definition_or_measurement_approach":"Adverse events recorded and graded according to protocol-specified criteria"}
- {"endpoint_text":"- 4. Incidence of cytokine-release related events (cytokine-release syndrome [CRS] and infusion-related reactions [IRRs]) according to the grading criteria in Lee (2014)","definition_or_measurement_approach":"CRS and IRRs graded using Lee (2014) grading criteria"}
- {"endpoint_text":"- 5. Changes in clinical laboratory values: hematology and biochemistry test results","definition_or_measurement_approach":"Laboratory hematology and biochemistry tests compared to baseline values"}
- {"endpoint_text":"- 6. Changes in vital signs, including systolic and diastolic blood pressure, respiratory rate, pulse rate, and body temperature","definition_or_measurement_approach":"Vital sign measurements recorded and compared to baseline"}
- {"endpoint_text":"- 7. Incidence of ECG abnormality","definition_or_measurement_approach":"ECG assessments for abnormalities recorded as incidence"}
- {"endpoint_text":"- 8. Total exposure (area under the concentration-time curve [AUC]) of glofitamab","definition_or_measurement_approach":"Pharmacokinetic measurement of AUC from serum concentration-time data"}
- {"endpoint_text":"- 9. Maximum serum concentration (Cmax) of glofitamab","definition_or_measurement_approach":"PK measurement of peak serum concentration (Cmax)"}
- {"endpoint_text":"- 10. Minimum serum concentration (Cmin) of glofitamab","definition_or_measurement_approach":"PK measurement of trough serum concentration (Cmin)"}
- {"endpoint_text":"- 11. Clearance (CL) of glofitamab","definition_or_measurement_approach":"PK parameter clearance derived from concentration-time data"}
- {"endpoint_text":"- 12. Volume of distribution (Vz) of glofitamab","definition_or_measurement_approach":"PK parameter volume of distribution derived from concentration-time data"}
- {"endpoint_text":"- 13. Independent Review Committee (IRC)-assessed CR rate using Lugano criteria","definition_or_measurement_approach":"Complete response (CR) rate assessed by an Independent Review Committee using Lugano 2014 Classification"}
Secondary endpoints
- {"endpoint_text":"- 1. Investigator (INV)-assessed CR rate (Lugano classification)","definition_or_measurement_approach":"Investigator-assessed complete response rate using Lugano classification"}
- {"endpoint_text":"- 2. IRC-assessed overall response rate (ORR) (Lugano classification)","definition_or_measurement_approach":"Overall response rate assessed by IRC using Lugano classification"}
- {"endpoint_text":"- 3. INV-assessed ORR (Lugano classification)","definition_or_measurement_approach":"Investigator-assessed ORR using Lugano classification"}
- {"endpoint_text":"- 4. IRC - and INV-assessed duration of complete response (Lugano Classification)","definition_or_measurement_approach":"Duration of complete response assessed by IRC and Investigator per Lugano criteria"}
- {"endpoint_text":"- 5. IRC- and INV-assessed duration of response (Lugano classification)","definition_or_measurement_approach":"Duration of response assessed by IRC and Investigator per Lugano criteria"}
- {"endpoint_text":"- 6. IRC-assessed progression-free survival (PFS) and INV-assessed PFS (Lugano classification)","definition_or_measurement_approach":"PFS assessed by IRC and Investigator using Lugano classification"}
- {"endpoint_text":"- 7. IRC-assessed time to first complete response (TFCR) (Lugano classification)","definition_or_measurement_approach":"Time to first complete response assessed by IRC per Lugano criteria"}
- {"endpoint_text":"- 8. INV-assessed TFCR (Lugano classification)","definition_or_measurement_approach":"Investigator-assessed time to first complete response per Lugano"}
- {"endpoint_text":"- 9. IRC-assessed time to first overall response (TFOR) (Lugano classification)","definition_or_measurement_approach":"Time to first overall response assessed by IRC per Lugano"}
- {"endpoint_text":"- 10. INV-assessed TFOR (Lugano classification)","definition_or_measurement_approach":"Investigator-assessed time to first overall response per Lugano"}
- {"endpoint_text":"- 11. Overall survival","definition_or_measurement_approach":"Overall survival measured from date of treatment to death from any cause"}
- {"endpoint_text":"- 12. Change from baseline in physical function, role function, and health-related quality of life European organization for research and treatment of cancer quality of Life questionnaire core 30 based on European organization for research and treatment of cancer quality of Life questionnaire core 30","definition_or_measurement_approach":"Change from baseline measured using EORTC QLQ-C30 scores"}
- {"endpoint_text":"- 13. Change from baseline in disease-related symptoms based on the functional assessment of cancer therapy-lymphoma scale","definition_or_measurement_approach":"Change from baseline measured using FACT-Lym scale"}
- {"endpoint_text":"- 14. Incidence of ADA formation and events related to immune complex deposition and activation","definition_or_measurement_approach":"Incidence of anti-drug antibodies (ADA) and related events assessed by immunogenicity assays and clinical reporting"}
Recruitment
- Planned Sample Size
- 560
- Recruitment Window Months
- 128
- Consent Approach
- Subject information sheets and informed consent forms are provided (multiple language versions and country-specific versions listed). An 'Informed consent form procedure' document is listed. Consent is provided by the participant; documents include material for pregnant partners. No explicit assent process for minors is stated in the available documents.
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 459
Belgium
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 02-08-2024
- Processing Time Days
- 14
- Number Of Sites
- 2
- Number Of Participants
- 38
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Hematology
- Contact Person Name
- Fritz Offner
- Contact Person Email
- fritz.offner@uzgent.be
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Hematology
- Contact Person Name
- Eric Van den Neste
- Contact Person Email
- eric.vandenneste@saintluc.uclouvain.be
Poland
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 04-08-2024
- Processing Time Days
- 16
- Number Of Sites
- 3
- Number Of Participants
- 31
Sites
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Ośrodek Badań Klinicznych Wczesnych Faz
- Contact Person Name
- Jan Zaucha
- Contact Person Email
- obkwf@uck.gda.pl
- Site Name
- Uniwersytecki Szpital Kliniczny W Poznaniu
- Department Name
- Oddzial Hematologii i Transplantacji Szpiku
- Contact Person Name
- Lidia Gil
- Contact Person Email
- sekretariat.hematologia@usk.poznan.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
- Department Name
- Klinika Hematologii, Terapii Komórkowych i Chorób Wewnętrznych
- Contact Person Name
- Tomasz Wróbel
- Contact Person Email
- Badaniakliniczne-khn@usk.wroc.pl
Denmark
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 06-08-2024
- Processing Time Days
- 18
- Number Of Sites
- 1
- Number Of Participants
- 43
Sites
- Site Name
- Rigshospitalet
- Department Name
- Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
- Contact Person Name
- Martin Hutchings
- Contact Person Email
- martin.hutchings@regionh.dk
Finland
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 02-08-2024
- Processing Time Days
- 14
- Number Of Sites
- 1
- Number Of Participants
- 9
Sites
- Site Name
- HUS-Yhtymae
- Department Name
- Helsinki University Hospital Cancer Center
- Contact Person Name
- Sirpa Leppä
- Contact Person Email
- sirpa.leppa@hus.fi
Spain
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 01-08-2024
- Processing Time Days
- 13
- Number Of Sites
- 6
- Number Of Participants
- 76
Sites
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Servicio de Hematologia
- Contact Person Name
- Joaquín Martínez López
- Contact Person Email
- jmarti01@ucm.es
- Site Name
- Hospital Germans Trias I Pujol
- Department Name
- Servicio de Hematologia
- Contact Person Name
- Juan Manuel Sancho Cía
- Contact Person Email
- jsancho@iconcologia.net
- Site Name
- Hospital Universitario Marques De Valdecilla
- Department Name
- Servicio de Hematologia
- Contact Person Name
- Sonia González de Villambrosia
- Contact Person Email
- sonia.glezdevillambrosi@scsalud.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Servicio de Hematologia
- Contact Person Name
- Francesc Bosch Albareda
- Contact Person Email
- fbosch@vhio.net
- Site Name
- Institut Catala D'oncologia
- Department Name
- Servicio de Hematologia
- Contact Person Name
- Anna Sureda Balari
- Contact Person Email
- asureda@iconcologia.net
- Site Name
- Hospital Del Mar
- Department Name
- Servicio de Hematologia
- Contact Person Name
- Ramón Díez-Feijoó Varela
- Contact Person Email
- rdiez-feijoo@psmar.cat
France
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 02-08-2024
- Processing Time Days
- 14
- Number Of Sites
- 5
- Number Of Participants
- 116
Sites
- Site Name
- Hospices Civils De Lyon
- Department Name
- Hématologie
- Contact Person Name
- Emmanuel Bachy
- Contact Person Email
- LS.RC-HEMATO-LY@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Hématologie
- Contact Person Name
- Roch Houot
- Contact Person Email
- roch.houot@chu-rennes.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Hématologie
- Contact Person Name
- Guillaume Cartron
- Contact Person Email
- g-cartron@chu-montpellier.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Hématologie
- Contact Person Name
- Franck Morschhauser
- Contact Person Email
- drs.promotion@chru-lille.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hématologie
- Contact Person Name
- Corinne Haioun
- Contact Person Email
- corinne.haioun@aphp.fr
Czechia
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 01-08-2024
- Processing Time Days
- 13
- Number Of Sites
- 1
- Number Of Participants
- 23
Sites
- Site Name
- Vseobecna Fakultni Nemocnice V Praze
- Department Name
- klinika hematologie
- Contact Person Name
- Marek Trněný
- Contact Person Email
- trneny@cesnet.cz
Italy
- Earliest CTIS Part Ii Submission Date
- 19-07-2024
- Latest Decision Or Authorization Date
- 07-08-2024
- Processing Time Days
- 19
- Number Of Sites
- 3
- Number Of Participants
- 123
Sites
- Site Name
- Humanitas Mirasole S.p.A.
- Department Name
- Dipartimento Oncologia e Ematologia
- Contact Person Name
- Carmelo Carlo-Stella
- Contact Person Email
- carmelo.carlostella@hunimed.eu
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- S. C. Ematologia
- Contact Person Name
- Paolo Corradini
- Contact Person Email
- paolo.corradini@unimi.it
- Site Name
- Azienda Unita Sanitaria Locale Della Romagna
- Department Name
- Dipartimento Oncoematologico - U.O.C. Oncologia
- Contact Person Name
- Monica Tani
- Contact Person Email
- monica.tani@auslromagna.it
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Endpoint Clinical Inc.
- Responsibilities
- IxRS Provider
- Name
- Syneos Health Netherlands B.V.
- Responsibilities
- code: 11
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- code: 4
- Name
- Iqvia Inc.
- Responsibilities
- Site Management Provider
- Name
- Q Squared Solutions Limited / Q Squared Solutions Holdings LLC
- Responsibilities
- Laboratory/assay and lab services (code: 4)
- Name
- Biotel Research LLC
- Responsibilities
- ECG Provider
Third parties
- {"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":"Other Third Party Duty","organisation_type":"Patient organisation/association"}
- {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IxRS Provider","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"code: 11","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"MicroCoat Biotechnologie GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Site Management Provider","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"GP Grenzach Produktions GmbH","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Biotel Research LLC","duties_or_roles":"ECG Provider","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"code: 13","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Glofitamab
- Active Substance
- GLOFITAMAB
- Modality
- Bispecific antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Not authorised
- Dose Levels
- Escalating doses; Part II starts when a dose of 810 µg (flat dose) is reached
- Maximum Dose
- 810 µg (flat dose)
- Investigational Product Name
- Columvi 10 mg concentrate for solution for infusion
- Active Substance
- GLOFITAMAB
- Modality
- Bispecific antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Authorised
- Dose Levels
- Escalating doses; Part II starts when a dose of 810 µg (flat dose) is reached
- Maximum Dose
- 810 µg (flat dose)
- Investigational Product Name
- Gazyvaro 1,000 mg concentrate for solution for infusion.
- Active Substance
- OBINUTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Authorised
- Investigational Product Name
- RoActemra 20 mg/mL concentrate for solution for infusion
- Active Substance
- TOCILIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Authorised (used as auxiliary/unauthorised AxMP in study)
- Combination Treatment
- Yes
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