Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors

NCT04925609 | Recruiting Phase 1 DMC

• 1 other identifier: ITCC-098
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 2

Brief Summary

This is an open-label, phase I-II dose-escalation and expansion study designed to define the recommended dose of brigatinib as monotherapy in pediatric and young adult patients with ALK+ ALCL, IMT or other solid tumors and to evaluate the pharmacokinetics (PK), (long-term) safety, and efficacy of brigatinib in these children.

Conditions

Anaplastic Large Cell Lymphoma, ALK-Positive; Inflammatory Myofibroblastic Tumor; Other Solid Tumor

Outcome Measures

Primary Outcomes (6)

• Phase 1: assess the MTD/RP2D regimen

  Phase 1: • To assess the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors. Dose-limiting toxicities (DLTs) during the first course of therapy. The RP2D is defined as the dose that results in equivalent (approximately ±20% of the adult values) PK exposure to 180 mg QD with a 7 day lead in of 90 mg QD in adults and with 0 or 1 DLT in 6 patients.

  2 years

• Phase 1: to characterize the PK of brigatinib

  Phase 1: • To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors: o maximum observed concentration (Cmax),

  2 years

• Phase 1: to characterize the PK of brigatinib

  Phase 1: • To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors: o area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast).

  2 years

• Phase 1: to characterize the PK of brigatinib

  Phase 1: * To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors: * time of first occurrence of maximum observed concentration (Tmax), T ½.

  2 years

• Phase 2: ORR in IMT

  • B1, ALK+ IMT: To establish the activity (ORR by RECIST 1.1, best response) of single agent brigatinib when administered to children with ALK+ IMT: Best response, defined as the percentage of patients with CR or PR according to RECIST 1.1 as best response during brigatinib treatment.

  2 years

• Phase 2: EFS in ALCL

  • B2, ALK+ ALCL: To establish the efficacy (EFS) of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without SCT in consolidation. EFS, defined as the time between start of study treatment and first event being progressive disease (according to IPNHL criteria), relapse, death of any cause and second malignancies.

  2 years

Study Arms (2)

Phase 1

OTHER

Phase 1: * To estimate the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors. * To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors. Note that: * If the MTD is not reached at the highest proposed test dose, no further dose-escalation will be performed. * Pediatric PK data, compared to exposure in adults, and cumulative toxicity, will be taken into consideration to determine the RP2D regimen.

Drug: Brigatinib

Phase 2

OTHER

Phase 2: • B1, ALK+ IMT: To establish the activity (ORR by RECIST 1.1) of single agent brigatinib when administered to children with ALK+ IMT. • B2, ALK+ ALCL: To establish the efficacy (EFS) of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without SCT in consolidation.

Drug: Brigatinib

Interventions

Brigatinib DRUG

Brigatinib is a second generation novel, orally administered, tyrosine kinase inhibitor (TKI) that potently inhibits activated variants of ALK and to a lesser extent ROS1.

Also known as: Alunbrig

Phase 1; Phase 2

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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. Note: for phase 1 only patients ≤18 years old will be eligible, A liquid formulation for children with a weight lower than 10 kg or for those that cannot swallow tablets is in development.
• Patients must have a confirmed diagnosis of cancer histologically 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.
• For 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 ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or
• o MRD-positivity by qualitative PCR for NPM-ALK prophase after one block 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 unresectable ALK+ IMT, or when surgery would imply severe mutilation may also be included, as well as metastatic disease.
• Patients with other solid tumors (excluding IMT) must have relapsed or refractory disease.
• For Phase 2, patients must have measurable and/or evaluable disease:
• Patients with ALCL must be relapsed/refractory. Refractory disease for ALCL is defined as:
• no response to ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or
• MRD-positivity by qualitative PCR for NPM-ALK prophase after one block ALCL99/other standard of care chemotherapy (before the second course of chemotherapy).
• Patients with R/R IMT Relapsed/refractory ALK+ IMT, or newly diagnosed, including advanced and metastatic, ALK+ IMT which cannot be surgically resected without causing mutilation
• Performance Status: Karnofsky performance status ≥40% for patients \>16 years of age or Lansky Play Scale ≥40% for patients ≤16 years of age.
• 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.

You may not qualify if:

• Patients receiving systemic treatment with strong or moderate CYP3A inhibitors or inducers within 14 days or five half-life times whichever the less prior to the first dose of study drug (refer to Section 5.2 for a list of example medications).
• Diagnosis of another concurrent primary malignancy.
• Clinically significant cardiovascular disease, including any of the following:
• Myocardial infarction or unstable angina within 6 months of study entry.
• History of or presence of heart block, and/or clinically significant ventricular or atrial arrhythmias.
• Uncontrolled hypertension defined as persistent elevation of systolic and/or diastolic blood pressures to ≥95th percentile based on age, sex, and height percentiles despite appropriate antihypertensive management.
• Planned non-protocol chemotherapy, radiation therapy, another investigational agent, or immunotherapy while patient is on study treatment.
• Any illness that affects gastrointestinal absorption.
• Ongoing or active systemic infection, active seropositive HIV, or known active hepatitis B or C infection.
• Any pre-existing condition or illness that, in the opinion of the investigator or sponsor, would compromise patient safety or interfere with the evaluation of the safety or efficacy of brigatinib.
• Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved).
• Uncontrolled seizure disorder (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs are eligible).

Sponsors & Collaborators

• Princess Maxima Center for Pediatric Oncology: lead
• Takeda: collaborator

Study Sites (2)

Institut Gustave Roussy

Paris, 94805, France

RECRUITING

Princess Máxima Center for Pediatric Oncology

Utrecht, Utrecht, 3584 CS, Netherlands

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Granuloma, Plasma Cell

Interventions

brigatinib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Granuloma; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michel Zwaan, Prof

  Princess Maxima Center for Pediatric Oncology in The Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maaike Boonstra

CONTACT

+31642055985; m.boonstra@prinsesmaximacentrum.nl

Gertruud Bakker

CONTACT

+31889727272; G.C.M.Bakker-7@prinsesmaximacentrum.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1: * To estimate the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors. * To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors. Note that: * If the MTD is not reached at the highest proposed test dose, no further dose-escalation will be performed. * Pediatric PK data, compared to exposure in adults, and cumulative toxicity, will be taken into consideration to determine the RP2D regimen. Phase 2: • B1, ALK+ IMT: To establish the activity (ORR by RECIST 1.1) of single agent brigatinib when administered to children with ALK+ IMT. • B2, ALK+ ALCL: To establish the efficacy (EFS) of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without SCT in consolidation.

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: June 14, 2021
• Study Start: August 18, 2022
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2033
• Last Updated: December 5, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: The CSR will be made available within 6 months upon study end.
• Access Criteria: A summary of the study results will be made public via clinicaltrials.gov as well as to Ethical committees/ Health Authorities and all participating patients by providing them through their treating physicians a patient letter with a summary of the results.

Locations

NL (1); FR (1)