Clinical trial • Phase I/II • Oncology
BRIGATINIB for Anaplastic large-cell lymphoma | Inflammatory myofibroblastic tumour | Other solid tumors
Phase I/II trial of BRIGATINIB for Anaplastic large-cell lymphoma | Inflammatory myofibroblastic tumour | Other solid tumors.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Anaplastic large-cell lymphoma | Inflammatory myofibroblastic tumour | Other solid tumors
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 03-10-2024
- First CTIS Authorization Date
- 31-10-2024
Trial design
None/Not specified-controlled, adaptive Phase I/II trial in Netherlands, France, Denmark and others.
- Comparator
- None/Not specified
- Adaptive
- True, dose-escalation in Phase 1 with DSMB selection of RP2D based on PK equivalence to adult exposure (approximately ±20%), DLT incidence (<2/6 patients at RP2D) and observed responses; interim safety/PK-driven decisions for RP2D.
- Biomarker Stratified
- True, biomarker: ALK positivity; strata: ALK+ ALCL | ALK+ IMT | ALK+ other solid tumors
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 11
Eligibility
Recruits 11 paediatric patients.
- Vulnerable Population
- Pediatric and adolescent participants are included (patients ≥1 and <26 years). The study materials include age-specific subject information sheets and informed consent forms for multiple age groups (e.g. minors under 7, 7-11, 12-17, young adults) and parent/guardian LAR forms; consent is provided by parents/legal guardians for minors with assent/age-appropriate information for children/adolescents as per those documents. Documents are available in multiple country/language versions (examples: FR, DE, NL, ES, IT, FI, SE, PL, CZ, DK, BE languages), indicating adapted consent/assent handling for vulnerable populations.
Inclusion criteria
- {"criterion_text":"- Patients must be ≥ 1 and < 26 years of age at the time of enrollment, and able to swallow brigatinib tablets at the time of enrollment, with a minimum weight of 10 kg.\n- Patients must have a histologically confirmed diagnosis of cancer at baseline. In patients where a repeat biopsy at relapse (or moment of refractory disease) is considered not feasible by the treating physician, archived material from diagnosis needs to be available for central review.\n- Patients are required to provide prior results showing an activating ALK aberration in the tumor per local laboratory results, and material needs to be available for central laboratory confirmation of ALK status. For ALK+ ALCL, detection of ALK with immunohistochemistry (IHC) is sufficient for inclusion, all others require molecular evidence of a ALK fusion gene or mutation by FISH, PCR or NGS. ALK detection will be confirmed centrally with FISH.\n- Phase 1: • Patients with ALCL must be relapsed/refractory or intolerant to standard therapies. Refractory disease for ALCL is defined as: o no response to at least one course of ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or o MRD-positivity by qualitative PCR for NPM-ALK after at least one course of ALCL99/other standard of care chemotherapy (before the second course of chemotherapy). • Patients with relapsed/refractory (R/R) IMT must not be suitable for curative surgical resection without causing mutilation. Newly diagnosed patients with locally advanced IMT, for whom surgery may not be feasible for close proximity to vital structures, without prior tumor-shrinkage, may also be included, as well as metastatic disease. • Patients with other solid tumors (excluding IMT) must have relapsed or refractory disease.\n- Phase 2: • Patients with ALCL must be relapsed/refractory. Refractory disease for ALCL is defined as: o no response to at least one course of ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or o MRD-positivity by qualitative PCR for NPM-ALK after at least one course of ALCL99/other standard of care chemotherapy (before the second course of chemotherapy). • Patients with R/R IMT Relapsed/refractory IMT, or newly diagnosed, including locally advanced and metastatic IMT which cannot be surgically resected without causing mutilation.\n- Performance Status: • Karnofsky performance status ≥40% for patients >16 years of age or Lansky Play Scale ≥40% for patients ≤16 years of age for ALCL patients in phase 2. • Karnofsky performance status ≥50% for patients >16 years of age or Lansky Play Scale ≥50% for patients ≤16 years of age, for IMT and other solid tumors and for ALCL patients in phase 1.\n- Patients must not be receiving other investigational medications (defined as medicinal products not yet approved for any indications, including alternative/herbal therapies) within 30 days of first dose of study drug or while on study.\n- Cohort B1R and B2R: Patients who were previously treated in the phase 1 or phase 2 part of this study, who completed brigatinib treatment as defined in this protocol, who responded to prior brigatinib treatment on protocol, and who developed a relapse or progression within 12 months after completion of brigatinib treatment (defined as per the EOT visit date)."}
Exclusion criteria
- {"criterion_text":"- Patients receiving systemic treatment with strong or moderate CYP3A inhibitors or inducers within 14 days or five half-lives, whichever the less, prior to the first dose of study drug (refer to Section 5.2 for a list of example medications).\n- Diagnosis of another concurrent primary malignancy."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Phase 1: dose-limiting toxicities (DLTs) during the first course of therapy.","definition_or_measurement_approach":"DLTs assessed during the first course of therapy in Phase 1 per protocol-defined DLT criteria."}
- {"endpoint_text":"- Phase 1: Brigatinib plasma PK parameters to be determined: o maximum observed concentration (Cmax), o time of first occurrence of maximum observed concentration (Tmax), o area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast).","definition_or_measurement_approach":"Plasma PK sampling to determine Cmax, Tmax and AUClast for brigatinib as specified in protocol."}
- {"endpoint_text":"- Phase 1: The RP2D will be selected by the DSMB and will be based on the dose that results in equivalent (approximately ±20% of the adult values) PK exposure to the adult comparator and with <2 out of 6 patients at this dose level present with a DLT and taking into account responses observed in phase 1.","definition_or_measurement_approach":"RP2D selection by DSMB using PK exposure comparison to adult values (≈±20%), DLT incidence threshold (<2/6 patients with DLT) and observed responses in Phase 1."}
- {"endpoint_text":"- Cohort B1: Overall response rate (ORR), defined as the percentage of patients with CR or PR according to RECIST 1.1 after 1 course and best ORR during brigatinib treatment.","definition_or_measurement_approach":"ORR measured per RECIST 1.1 as proportion of patients achieving CR or PR after one course and best response during treatment."}
- {"endpoint_text":"- Cohort B2: EFS (using the IPNHL response criteria), defined as the time between start of study treatment and first event being progressive disease, relapse, death of any cause and second malignancies, whatever happens first. Patients consolidated with HSCT will be censored.","definition_or_measurement_approach":"Event-free survival measured from treatment start to first event (progression, relapse, death, second malignancy) per IPNHL criteria; HSCT-consolidated patients censored."}
- {"endpoint_text":"- Cohort B1R: Overall response rate (ORR), defined as the percentage of patients with CR or PR according to RECIST 1.1 after 1 course and best ORR during brigatinib re-treatment.","definition_or_measurement_approach":"ORR on re-treatment measured per RECIST 1.1 as proportion with CR or PR after one course and best response during re-treatment."}
- {"endpoint_text":"- Cohort B2R: EFS (using the IPNHL response criteria), defined as the time between restart of study treatment and first event being progressive disease, relapse, death of any cause and second malignancies, whatever happens first. Patients consolidated with HSCT will be censored.","definition_or_measurement_approach":"Event-free survival from restart of treatment to first event (progression, relapse, death, second malignancy) per IPNHL criteria; HSCT-consolidated patients censored."}
Recruitment
- Planned Sample Size
- 54
- Recruitment Window Months
- 135
- Consent Approach
- Informed consent is handled with age-appropriate ICFs: parent/guardian LAR consent for minors and assent/information sheets for children and adolescents; specific ICFs exist for multiple age bands (e.g. under 7, 7-11, 12-17, young adults) and for retreatment. Documents are provided in country/language-specific versions (examples include French, German, Dutch, Spanish, Italian, Finnish, Swedish, Polish, Czech, Danish, Belgian language variants), indicating consent and assent are managed per local regulations and age group.
Geography
- Total Number Of Sites
- 28
- Total Number Of Participants
- 54
Netherlands
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 16-10-2025
- Processing Time Days
- 356
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Department Name
- Paediatric Oncology
- Principal Investigator Name
- Natasha van Eijkelenburg
- Principal Investigator Email
- n.k.a.vaneijkelenburg@prinsesmaximacentrum.nl
- Contact Person Name
- Natasha van Eijkelenburg
- Contact Person Email
- n.k.a.vaneijkelenburg@prinsesmaximacentrum.nl
France
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 355
- Number Of Sites
- 6
- Number Of Participants
- 8
Sites
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Hématologie - Oncologie Pédiatrique
- Principal Investigator Name
- Marie-Laure Couec
- Principal Investigator Email
- marielaure.couec@chu-nantes.fr
- Contact Person Name
- Marie-Laure Couec
- Contact Person Email
- marielaure.couec@chu-nantes.fr
- Site Name
- Pellegrin Hospital
- Department Name
- Unité d'Hématologie et d’Oncologie Pédiatriques
- Principal Investigator Name
- Stephane Ducassou
- Principal Investigator Email
- stephane.ducassou@chu-bordeaux.fr
- Contact Person Name
- Stephane Ducassou
- Contact Person Email
- stephane.ducassou@chu-bordeaux.fr
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Hématologie et oncologie pédiatrique
- Principal Investigator Name
- Nicolas Andre
- Principal Investigator Email
- nicolas.andre@ap-hm.fr
- Contact Person Name
- Nicolas Andre
- Contact Person Email
- nicolas.andre@ap-hm.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- Cancérologie de l’Enfant et de l’Adolescent
- Principal Investigator Name
- Veronique Minard-Colin
- Principal Investigator Email
- veronique.minard@gustaveroussy.fr
- Contact Person Name
- Veronique Minard-Colin
- Contact Person Email
- veronique.minard@gustaveroussy.fr
- Site Name
- CHRU De Nancy
- Department Name
- Onco-hematologie pediatrique
- Principal Investigator Name
- Cecile Pochon
- Principal Investigator Email
- c.pochon@chru-nancy.fr
- Contact Person Name
- Cecile Pochon
- Contact Person Email
- c.pochon@chru-nancy.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Hématologie et oncologie pédiatrique
- Principal Investigator Name
- Nathalie Garnier
- Principal Investigator Email
- nathalie.garnier@ihope.fr
- Contact Person Name
- Nathalie Garnier
- Contact Person Email
- nathalie.garnier@ihope.fr
Denmark
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 355
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Rigshospitalet
- Department Name
- Dept. of Pediactrics and Adolescent Medicine
- Principal Investigator Name
- Ruta Tuckuviene
- Principal Investigator Email
- ruta.tuckuviene@regionh.dk
- Contact Person Name
- Ruta Tuckuviene
- Contact Person Email
- ruta.tuckuviene@regionh.dk
Netherlands
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 16-10-2025
- Processing Time Days
- 356
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Department Name
- Paediatric Oncology
- Principal Investigator Name
- Natasha van Eijkelenburg
- Principal Investigator Email
- n.k.a.vaneijkelenburg@prinsesmaximacentrum.nl
- Contact Person Name
- Natasha van Eijkelenburg
- Contact Person Email
- n.k.a.vaneijkelenburg@prinsesmaximacentrum.nl
Belgium
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 355
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Pediatric Hemato-Oncology & Stem Cell Transplantation
- Principal Investigator Name
- Barbara De Moerloose
- Principal Investigator Email
- barbara.demoerloose@uzgent.be
- Contact Person Name
- Barbara De Moerloose
- Contact Person Email
- barbara.demoerloose@uzgent.be
Germany
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 355
- Number Of Sites
- 7
- Number Of Participants
- 6
Sites
- Site Name
- University Hospital Cologne AöR
- Department Name
- Experimental Pediatric Oncology, University Children's Hospital
- Principal Investigator Name
- Matthias Fischer
- Principal Investigator Email
- matthias.fischer@uk-koeln.de
- Contact Person Name
- Matthias Fischer
- Contact Person Email
- matthias.fischer@uk-koeln.de
- Site Name
- Universitaetsklinikum Augsburg
- Department Name
- Children’s Cancer Center
- Principal Investigator Name
- Michael Fruhwald
- Principal Investigator Email
- michael.fruehwald@uk-augsburg.de
- Contact Person Name
- Michael Fruhwald
- Contact Person Email
- michael.fruehwald@uk-augsburg.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Department of Pediatric Oncology and Hematology - Early Phase Clinical Trial Unit
- Principal Investigator Name
- Anne Thorwarth
- Principal Investigator Email
- Anne.thorwarth@charite.de
- Contact Person Name
- Anne Thorwarth
- Contact Person Email
- Anne.thorwarth@charite.de
- Site Name
- Universitaetsklinikum Muenster AöR
- Department Name
- Klinik für Kinder- und Jugendmedizin Pädiatrische Hämatologie und Onkologie
- Principal Investigator Name
- Birgit Burkhardt
- Principal Investigator Email
- birgit.burkhardt@ukmuenster.de
- Contact Person Name
- Birgit Burkhardt
- Contact Person Email
- birgit.burkhardt@ukmuenster.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Department of Pediatric Oncology and Hematology
- Principal Investigator Name
- Ivana Eikelberg
- Principal Investigator Email
- Ivana.Eikelberg@uk-essen.de
- Contact Person Name
- Ivana Eikelberg
- Contact Person Email
- Ivana.Eikelberg@uk-essen.de
- Site Name
- Universitaetsklinikum Frankfurt AöR
- Department Name
- Klinik für Kinder- und Jegendmedizin
- Principal Investigator Name
- Marie Luckowitsch
- Principal Investigator Email
- Marie.Luckowitsch@unimedizin-ffm.de
- Contact Person Name
- Marie Luckowitsch
- Contact Person Email
- Marie.Luckowitsch@unimedizin-ffm.de
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Pediatric Hematology and Oncology
- Principal Investigator Name
- Wilhelm Woessmann
- Principal Investigator Email
- w.woessmann@uke.de
- Contact Person Name
- Wilhelm Woessmann
- Contact Person Email
- w.woessmann@uke.de
Italy
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 355
- Number Of Sites
- 4
- Number Of Participants
- 5
Sites
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Pediatria Oncologica
- Principal Investigator Name
- Michela Casanova
- Principal Investigator Email
- michela.casanova@istitutotumori.mi.it
- Contact Person Name
- Michela Casanova
- Contact Person Email
- michela.casanova@istitutotumori.mi.it
- Site Name
- Azienda Ospedaliera di Padova
- Department Name
- U.O.C. Oncoematologia Pediatrica
- Principal Investigator Name
- Marta Pillon
- Principal Investigator Email
- marta.pillon@unipd.it
- Contact Person Name
- Marta Pillon
- Contact Person Email
- marta.pillon@unipd.it
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Department Name
- Clinica Pediatrica
- Principal Investigator Name
- Alessandra Sala
- Principal Investigator Email
- alessandra.sala@irccs-sangerardo.it
- Contact Person Name
- Alessandra Sala
- Contact Person Email
- alessandra.sala@irccs-sangerardo.it
- Site Name
- Ospedale Pediatrico Bambino Gesu
- Department Name
- Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
- Principal Investigator Name
- Franco Locatelli
- Principal Investigator Email
- franco.locatelli@opbg.net
- Contact Person Name
- Franco Locatelli
- Contact Person Email
- franco.locatelli@opbg.net
Spain
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 355
- Number Of Sites
- 3
- Number Of Participants
- 6
Sites
- Site Name
- Hospital Infantil Universitario Nino Jesus
- Department Name
- Department of Onco-Haematology and Haematopoietic Transplant.
- Principal Investigator Name
- Maitane Andion
- Principal Investigator Email
- maitane.andion@salud.madrid.org
- Contact Person Name
- Maitane Andion
- Contact Person Email
- maitane.andion@salud.madrid.org
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Department of Pediatric Oncology.
- Principal Investigator Name
- Adela Cañete
- Principal Investigator Email
- canyete_ade@gva.es
- Contact Person Name
- Adela Cañete
- Contact Person Email
- canyete_ade@gva.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Department of Pediatric Oncology and Haematology.
- Principal Investigator Name
- Raquel Hladun
- Principal Investigator Email
- raquel.hladun@vallhebron.cat
- Contact Person Name
- Raquel Hladun
- Contact Person Email
- raquel.hladun@vallhebron.cat
Czechia
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 14-10-2025
- Processing Time Days
- 354
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Fakultni Nemocnice V Motole
- Department Name
- Klinika detske hematologie a onkologie 2. LF UK
- Principal Investigator Name
- Lucie Sramkova
- Principal Investigator Email
- Lucie.Sramkova@fnmotol.cz
- Contact Person Name
- Lucie Sramkova
- Contact Person Email
- Lucie.Sramkova@fnmotol.cz
Poland
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 17-10-2025
- Processing Time Days
- 357
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Uniwersytet Jagiellonski Collegium Medicum
- Department Name
- Klinika Onkologii i Hematologii Dziecięcej
- Principal Investigator Name
- Aleksandra Wieczorek
- Principal Investigator Email
- a.wieczorek@uj.edu.pl
- Contact Person Name
- Aleksandra Wieczorek
- Contact Person Email
- a.wieczorek@uj.edu.pl
Finland
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 13-10-2025
- Processing Time Days
- 353
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- HUS-Yhtymae
- Department Name
- Hemat.Onco & SCT
- Principal Investigator Name
- Antti Kyronlahti
- Principal Investigator Email
- Antti.Kyronlahti@hus.fi
- Contact Person Name
- Antti Kyronlahti
- Contact Person Email
- Antti.Kyronlahti@hus.fi
Austria
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 13-10-2025
- Processing Time Days
- 353
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- St. Anna Kinderspital GmbH
- Department Name
- Department of Pediatric Hematology and Oncology
- Principal Investigator Name
- Andishe Attarbaschi
- Principal Investigator Email
- andishe.attarbaschi@stanna.at
- Contact Person Name
- Andishe Attarbaschi
- Contact Person Email
- andishe.attarbaschi@stanna.at
Sweden
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 06-05-2026
- Processing Time Days
- 558
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
- Department Name
- Barncancercentrum
- Principal Investigator Name
- Karin Mellgren
- Principal Investigator Email
- karin.mellgren@vgregion.se
- Contact Person Name
- Karin Mellgren
- Contact Person Email
- karin.mellgren@vgregion.se
Sponsor
Primary sponsor
- Full Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Netherlands
Third parties
- {"country":"Netherlands","full_name":"Allucent (NL) B.V.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"","full_name":"Takeda","duties_or_roles":"Monetary support","organisation_type":""}
Investigational products
- Investigational Product Name
- BRIGATINIB (oral solution)
- Active Substance
- BRIGATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Investigational Product Name
- Alunbrig 180 mg film-coated tablets
- Active Substance
- BRIGATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- EU/1/18/1264/009
- Investigational Product Name
- Alunbrig 90 mg film-coated tablets
- Active Substance
- BRIGATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- EU/1/18/1264/006
- Investigational Product Name
- Alunbrig 30 mg film-coated tablets
- Active Substance
- BRIGATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- EU/1/18/1264/001
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