Clinical trial • Phase I/II • Oncology
ZILOVERTAMAB VEDOTIN for B-cell acute lymphoblastic leukemia|Diffuse large B-cell lymphoma|Burkitt lymphoma|Neuroblastoma|Ewing sarcoma
Phase I/II trial of ZILOVERTAMAB VEDOTIN for B-cell acute lymphoblastic leukemia|Diffuse large B-cell lymphoma|Burkitt lymphoma|Neuroblastoma|Ewing sarcom…
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- B-cell acute lymphoblastic leukemia|Diffuse large B-cell lymphoma|Burkitt lymphoma|Neuroblastoma|Ewing sarcoma
- Trial Stage
- Phase I/II
- Drug Modality
- ADC|Monoclonal antibody
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 29-11-2023
- First CTIS Authorization Date
- 15-04-2024
Trial design
adaptive Phase I/II trial across 26 sites in Italy, Slovakia, Spain and others.
- Adaptive
- True - Part 1 includes a dose-escalation design evaluating dose-limiting toxicities (DLTs) with dose modifications and interim safety assessments (adaptive escalation based on observed DLTs/AEs).
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 63
Eligibility
Recruits 63 paediatric patients.
- Vulnerable Population
- The trial includes pediatric and young adult participants (population includes birth through <18 years for some indications and up to 25 years for Ewing sarcoma). Vulnerable populations are selected (isVulnerablePopulationSelected = true). Consent/assent handling: parental/legal guardian consent is required for minors; age-appropriate assent and consent documents are provided (numerous country-specific informed consent and assent forms listed for age groups such as 02-05 yr, 06-09 yr, 06-11 yr, 10-14 yr, 12-17 yr, 13-17 yr, and versions for parent/guardian and adult participants). Country- and language-specific consent and assent materials are available as reflected in the submitted ICF/assent documents.
Inclusion criteria
- {"criterion_text":"- For hematological malignancies: Confirmed diagnosis of B-precursor B-ALL or DLBCL/Burkitt lymphoma according to World Health Organization (WHO) classification of neoplasms of the lymphoid tissues (As of protocol Amendment 4, in countries in the European Economic Area [EEA], the substudy will not enroll participants with hematological malignancies)\n- For solid tumor malignancies: Histologically confirmed diagnosis of neuroblastoma or Ewing sarcoma (As of protocol Amendment 4, in countries in the European Economic Area [EEA], the substudy will only enroll participants with diagnosis of Ewing sarcoma)"}
Exclusion criteria
- {"criterion_text":"- Has history of solid organ transplant.\n- Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities.\n- Has ongoing, chronic corticosteroid therapy (exceeding 10 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 4 weeks before Cycle 1 Day 1 (C1D1).\n- Has received a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 7 days or a strong CYP3A4 inducer within 14 days before the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor or inducer during the study intervention period and for 30 days after the last dose of study intervention\n- Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention (except for prophylactic intrathecal chemotherapy and/or cytoreductive therapy with steroids/hydroxyurea.\n- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.\n- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.\n- Has known additional malignancy that is progressing or has required active treatment within the past 1 year.\n- Has active infection requiring systemic therapy.\n- Has known history of Hepatitis B or known active Hepatitis C virus infection.\n- Participants who have not adequately recovered from major surgery or have ongoing surgical complications.\n- Has clinically significant (ie, active) cardiovascular disease.\n- Known history of liver cirrhosis.\n- Has ongoing Grade >1 peripheral neuropathy.\n- Has demyelinating form of Charcot-Marie-Tooth disease.\n- Has been diagnosed with Down syndrome.\n- Has ongoing graft-versus-host disease (GVHD) of any grade or receiving systemic GVHD treatment or prophylaxis.\n- Has history of human immunodeficiency virus (HIV) infection.\n- Has contraindication or hypersensitivity to any of the study intervention components."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma","definition_or_measurement_approach":""}
Secondary endpoints
- {"endpoint_text":"- Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 2: Number of Participants Who Receive Dose Modification Due to AEs","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Incidence of Antidrug antibodies (ADAs) to Zilovertamab Vedotin","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Duration of Response (DOR)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT","definition_or_measurement_approach":""}
- {"endpoint_text":"- Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)","definition_or_measurement_approach":""}
Recruitment
- Planned Sample Size
- 63
- Recruitment Window Months
- 60
- Consent Approach
- Informed consent is obtained from parents/legal guardians for minors; age-appropriate assent forms are provided for children and adolescents. Multiple country-specific consent and assent forms are submitted (documents for adult consent, parent/guardian consent, and assent for age bands such as 02-05 yr, 06-09 yr, 06-11 yr, 10-14 yr, 12-17 yr, 13-17 yr). Optional/ancillary consent documents (e.g., pregnancy follow-up, genetic consent, data privacy forms) are also provided. Consent materials are available in country-specific languages as indicated by the submitted ICF/assent documents.
Geography
- Total Number Of Sites
- 26
- Total Number Of Participants
- 50
Italy
- Earliest CTIS Part Ii Submission Date
- 21-12-2023
- Latest Decision Or Authorization Date
- 11-11-2025
- Processing Time Days
- 691
- Number Of Sites
- 3
- Number Of Participants
- 8
Sites
- Site Name
- Azienda Ospedaliera Universitaria Citta' Della Salute E Della Scienza Di Torino
- Department Name
- S.C. Oncoematologia Pediatrica
- Contact Person Name
- Franca Fagioli
- Contact Person Email
- franca.fagioli@unito.it
- Site Name
- Bambino Gesu Childrens Hospital
- Department Name
- Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
- Contact Person Name
- Franco Locatelli
- Contact Person Email
- franco.locatelli@opbg.net
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- S.C. Pediatria Oncologica
- Contact Person Name
- Michela Casanova
- Contact Person Email
- michela.casanova@istitutotumori.mi.it
Slovakia
- Earliest CTIS Part Ii Submission Date
- 14-03-2025
- Latest Decision Or Authorization Date
- 22-10-2025
- Processing Time Days
- 222
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Narodny Ustav Detskych Chorob
- Department Name
- Klinika detskej hematologie a onkologie
- Contact Person Name
- Alexandra Kolenova
- Contact Person Email
- alexandra.kolenova@nudch.eu
Spain
- Earliest CTIS Part Ii Submission Date
- 14-03-2024
- Latest Decision Or Authorization Date
- 05-03-2026
- Processing Time Days
- 722
- Number Of Sites
- 4
- Number Of Participants
- 9
Sites
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Onco hematologia pediatrica
- Contact Person Name
- Antonio Juan Ribelles
- Contact Person Email
- juan_antrib@gva.es
- Site Name
- Hospital Infantil Universitario Nino Jesus
- Department Name
- Pediatric
- Contact Person Name
- Alba Rubio San Simón
- Contact Person Email
- alba.rubio@salud.madrid.org
- Site Name
- Sant Joan De Deu Barcelona Hospital
- Department Name
- Oncological Pediatric Unit
- Contact Person Name
- Jaume Mora Graupera
- Contact Person Email
- jaume.mora@sjd.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Pediatric Oncology and Hematology Department
- Contact Person Name
- Raquel Hladun Alvaro
- Contact Person Email
- raquel.hladun@vallhebron.cat
Netherlands
- Earliest CTIS Part Ii Submission Date
- 18-03-2024
- Latest Decision Or Authorization Date
- 17-02-2026
- Processing Time Days
- 702
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Department Name
- Kinderoncologie
- Contact Person Name
- Natasha van Eijkelenburg
- Contact Person Email
- trialsupport@prinsesmaximacentrum.nl
Sweden
- Earliest CTIS Part Ii Submission Date
- 14-03-2024
- Latest Decision Or Authorization Date
- 05-02-2026
- Processing Time Days
- 694
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vastra Gotalandsregionen
- Department Name
- Barncancercentrum
- Contact Person Name
- Karin Mellgren
- Contact Person Email
- karin.mellgren@vgregion.se
France
- Earliest CTIS Part Ii Submission Date
- 23-02-2024
- Latest Decision Or Authorization Date
- 22-01-2026
- Processing Time Days
- 699
- Number Of Sites
- 5
- Number Of Participants
- 8
Sites
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Oncologie-Hématologie pédiatrique
- Contact Person Name
- Morgane Cleirec
- Contact Person Email
- morgane.cleirec@chu-nantes.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Unité d'onco- hematologie pédiatrique
- Contact Person Name
- Stéphane Ducassou
- Contact Person Email
- stephane.ducassou@chu-bordeaux.fr
- Site Name
- Centre Leon Berard
- Department Name
- Institut d’Hématologie et d’Oncologie Pédiatrique(IHOPe)
- Contact Person Name
- Nadege Corradini
- Contact Person Email
- nadege.corradini@ihope.fr
- Site Name
- Assistance Publique Hopitaux De Marseille
- Department Name
- Service d'immunologie hématologie et Oncologie Pédiatrique
- Contact Person Name
- Nicolas André
- Contact Person Email
- nicolas.andre@ap-hm.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- Cancérologie Enfant et Adolescent
- Contact Person Name
- Pablo Berlanga
- Contact Person Email
- pablo.berlanga@gustaveroussy.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 14-03-2024
- Latest Decision Or Authorization Date
- 10-02-2026
- Processing Time Days
- 699
- Number Of Sites
- 5
- Number Of Participants
- 4
Sites
- Site Name
- Universitaet Muenster
- Department Name
- Pädiatrische Hämatologie und Onkologie
- Contact Person Name
- Claudia Rössig
- Contact Person Email
- paedonc@ukmuenster.de
- Site Name
- Justus-Liebig-Universitaet Giessen
- Department Name
- Zentrum für Kinderheilkunde
- Contact Person Name
- Christine Mauz-Körholz
- Contact Person Email
- hodgkin@paediat.med.uni-giessen.de
- Site Name
- Universitaetsklinikum Tuebingen AöR
- Department Name
- Abteilung für päd. Hämatologie und Onkologie
- Contact Person Name
- Martin Ebinger
- Contact Person Email
- Martin.Ebinger@med.uni-tuebingen.de
- Site Name
- University Hospital Cologne AöR
- Department Name
- Pädiatrische Onkologie und Hämatologie
- Contact Person Name
- Matthias Fischer
- Contact Person Email
- matthias.fischer@uk-koeln.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Klinik für Pädiatrie m. S. Onkologie und Hämatologie
- Contact Person Name
- Anne Thorwarth
- Contact Person Email
- cathrin.schmeller@charite.de
Hungary
- Earliest CTIS Part Ii Submission Date
- 22-02-2024
- Latest Decision Or Authorization Date
- 13-02-2026
- Processing Time Days
- 722
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Semmelweis University
- Department Name
- Gyermekgyógyászati Klinika, Tűzoltó utcai részleg
- Contact Person Name
- Andrea Ponyi
- Contact Person Email
- ponyi.andrea@gyerekklinika.com
Belgium
- Earliest CTIS Part Ii Submission Date
- 13-03-2024
- Latest Decision Or Authorization Date
- 25-02-2026
- Processing Time Days
- 715
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Pediatric Oncology
- Contact Person Name
- Bram De Wilde
- Contact Person Email
- bram.dewilde@uzgent.be
Denmark
- Earliest CTIS Part Ii Submission Date
- 18-03-2024
- Latest Decision Or Authorization Date
- 02-02-2026
- Processing Time Days
- 687
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Rigshospitalet
- Department Name
- Klinisk Forsøgsenhed for Børn og Unge med Kræft Afdeling for Børn og Unge
- Contact Person Name
- Ruta Tuckuviene
- Contact Person Email
- ruta.tuckuviene@regionh.dk
Czechia
- Earliest CTIS Part Ii Submission Date
- 13-03-2024
- Latest Decision Or Authorization Date
- 24-02-2026
- Processing Time Days
- 714
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- Fakultni Nemocnice Brno
- Department Name
- Klinika dětské onkologie
- Contact Person Name
- Peter Múdry
- Contact Person Email
- mudry.peter@fnbrno.cz
- Site Name
- Fakultni Nemocnice V Motole
- Department Name
- Klinika dětské hematologie a onkologie
- Contact Person Name
- Michaela Čepelová
- Contact Person Email
- Michaela.Cepelova@fnmotol.cz
Greece
- Earliest CTIS Part Ii Submission Date
- 15-03-2024
- Latest Decision Or Authorization Date
- 02-02-2026
- Processing Time Days
- 690
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Nosokomeio Paidon I Agia Sofia
- Department Name
- 1st Pathology Clinic-Department of Paediatric Oncology/Heamatology
- Contact Person Name
- Antonios Kattamis
- Contact Person Email
- ankatt@med.uoa.gr
Sponsor
Primary sponsor
- Full Name
- Merck Sharp & Dohme LLC
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- code: 4
- Name
- Parexel International Corp.
- Responsibilities
- Medical information (Physician Consulting)
- Name
- Eresearchtechnology Inc.
- Responsibilities
- central imaging
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- code: 3
- Name
- Covance Central Laboratory Services Inc.
- Responsibilities
- central laboratory (code: 4)
- Name
- Perceptive Eclinical Limited
- Responsibilities
- EUB Call center and medical escalation service
- Name
- Infinity Biologix LLC
- Responsibilities
- DNA extraction of buccal swabs and sample storage
Third parties
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Medical information (Physician Consulting)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"central imaging","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Covance Central Laboratory Services Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"EUB Call center and medical escalation service","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"DNA extraction of buccal swabs and storage of samples until an anlysis lab is identified.","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Zilovertamab vedotin
- Active Substance
- ZILOVERTAMAB VEDOTIN
- Modality
- ADC|Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- Investigational product (IMP11011/00003)
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