A Phase I/II study of Brigatinib in pediatric and young adult patients with ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or other solid tumors

Phase 2

Recruiting

• Conditions: ALK+ ALCL, IMT en andere ALK+ tumoren; ALK positive tumors; 10024324

• Registration Number: NL-OMON50304
• Lead Sponsor: Prinses Máxima Centrum voor Kinderoncologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

1. Patients must be >=1 and < 26 years of age at the time of enrollment, and
able to swallow brigatinib tablets
Note 1: for phase 1 only patients < 18 years old will be eligible, note a
liquid formulation for children who cannot swallow tablets is in development.
Note 2: for the Netherlands only, minimum age is >= 5 years.
Note 3: for the Czech Republic only, minimum age is >= 4 years.
2. Patients must have a histologically confirmed diagnosis of cancer at baseline
3. 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
4. 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 at least one course of ALCL99/other standard of care
chemotherapy (SD or PD ), and/or
o MRD-positivity by qualitative PCR for NPM-ALK after at least one course
ALCL99/other standard of care chemotherapy (before the second course of
chemotherapy).
• Patients with relapsed/refractory (R/R) or newly diagnosed IMT must not be
suitable for curative surgical resection without causing severe mutilation or
risk associated with organ involvement, or have metastatic disease.
• Patients with other solid tumors (excluding IMT) must have relapsed or
refractory disease .
• Only patients >=1 and < 18 years will be eligible for phase 1. For the
Netherlands only, minimum age is >= 5 years

5. For Phase 2, patients must have measurable and/or evaluable disease:
• Patients with ALCL must be relapsed/refractory as defined.
o No response to at least one course of ALCL99/other standard of care
chemotherapy (SD or PD), 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.
6. 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.
7. Patients must not be receiving other investigational medications within 30
days of first dose of study drug or while on study.
9. Patients must have recovered to Grade <2 NCI CTCAE v5.0 or to baseline, from
any nonhematologic toxicities
10. Patients must meet the organ function and system function requirements as
stated below:
• Patients must have adequate renal and hepatic function
• No clinical, radiological or laboratory evidence of pancreatitis
• Absolute neutrophil count: >=0.75 × 10 9/L, except in case of macrophage
activation syndrome (MAS) or bone marrow involvement.
• Platelet count
o In phase 1: Platelet count: >=75 × 10^9/ L, except in case of MAS or bone
marrow involvement
o In phase 2: : Platelet count: >=75 × 10^9/ L, except in case of MAS or bone
marrow involvement. For patients

Exclusion Criteria

1. 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).
2. Diagnosis of another concurrent primary malignancy.
3. 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.
4. Planned non-protocol chemotherapy, radiation therapy, another
investigational agent, or immunotherapy while patient is on study treatment.
5. Any illness that affects gastrointestinal absorption.
6. Ongoing or active systemic infection, active seropositive HIV, or known
active hepatitis B or C infection.
7. 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.
8. Patients with rare hereditary problems of galactose intolerance, total
lactase deficiency or glucose-galactose malabsorption.
9. 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 and
causative have resolved).
10. 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).
11. Patients with electrolytes imbalances >= grade 2 NCI CTCAE v5.0 are not
eligible (supplementation or medical intervention is allowed to correct
electrolyte imbalance before inclusion).
12. Patients with uncontrolled diabetes, i.e. patients with persistent
hyperglycemia >= grade 2 NCI CTCAE v5.0 despite well conducted treatment with
either oral anti glycemic agent and/or insulin are not eligible (patients with
well controlled diabetes with either insulin or oral anti glycemic agents are
eligible).

Study & Design

• Study Type: Interventional
• Study Design: Not specified