Phase I/II study of Brigatinib as monotherapy in pediatric and young adult patients with anaplastic large cell lymphoma (ALCL) ALK-positive, inflammatory myofibroblastic tumors (IMT), or other solid tumors - BrigaPED Study

France, Netherlands (ICTRP)

Identifiant de l'essai ICTRP
NCT04925609 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
non disponible

Titre académique
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 (ICTRP)

Titre public
Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors (ICTRP)

Maladie en cours d'investigation
Inflammatory Myofibroblastic Tumor
Other Solid Tumor
Anaplastic Large Cell Lymphoma, ALK-Positive
(ICTRP)

Intervention étudiée
Drug: Brigatinib
(ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Other. Masking: None (Open Label). (ICTRP)

Critères d'inclusion/exclusion

Inclusion Criteria:

1. 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.

2. 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.

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. 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.

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 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.

5. 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

6. Performance Status: Karnofsky performance status =40% for patients >16 years of age or
Lansky Play Scale =40% for patients =16 years of age.

7. 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.

8. For patients receiving prior therapy:

- Patients who already received previous treatment with ALK inhibitors except for
brigatinib can be included in this study.

- Patients must have recovered to Grade <2 NCI CTCAE v5.0 or to baseline, from any
nonhematologic toxicities (except alopecia and peripheral neuropathy) due to
previous therapy.

- Patients who relapsed while receiving cytotoxic therapy: at least 14 days must
have passed since the completion of the last dose of chemotherapy before the
first dose of brigatinib can be given.

- Patients who have experienced relapse after a prior HSCT are eligible, provided
they have no evidence of acute or chronic graft-versus-host disease (GVHD), are
not receiving GVHD prophylaxis or treatment, and are at least 45 days
posttransplant at the time of enrollment.

- Hematopoietic growth factors: before the first dose of brigatinib, at least 7
days must have passed since completion of therapy with granulocyte
colony-stimulating factor or other growth factors, and at least 14 days must have
passed since completion of therapy with pegfilgrastim.

- Biologics and Targeted Therapies:

o Immunotherapy: Before the first dose of brigatinib, at least 30 days must have
passed after the completion of any type of immunotherapy, (i.e. monoclonal
antibodies [anti-PD1/PDL1], tumor vaccines, chimeric antigen receptor [CAR] T
cells, etc.).

o Other: before the first dose of brigatinib, at least 7 days must have passed
since the last dose of a biologic agent. For agents that have known adverse
events (AEs) occurring beyond 7 days after administration, this period must be
extended beyond the time during which AEs are known to occur. The duration of
this interval must be discussed with the sponsor's medical monitor/designee.

o Immunosuppressive therapy: Before the first dose of brigatinib, at least 14
days must have passed after the completion of immunosuppressive therapy
(including regimens following stem cell transplant).

o For symptomatic patients that urgently need relief (i.e. airway obstruction),
therapeutic doses of corticosteroids may be administered for a short course (up
to 5 days).

o Radiotherapy (XRT): No washout period is necessary for radiation given to any
extramedullary site other than the CNS and lungs; =45 days must have passed if
patient received prior total body irradiation or craniospinal or cranial XRT; =28
days must have passed if patient received radiotherapy to the lung. For patients
receiving XRT to both lungs, or in case of stereotactic radiotherapy, the PIs
should be consulted before inclusion.

9. Patients must meet the organ function and system function requirements as stated
below:

- Patients must have adequate renal and hepatic function as indicated by the
following laboratory values:

o Patient's serum creatinine must be = 1.5 x institutional upper limit of normal
(ULN) according to age. If the serum creatinine is greater than 1.5 x
institutional ULN, the patient must have a radioisotope GFR = 70mL/min/1.73m2

- Adequate liver function defined as: direct bilirubin (ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
Phase 2: ORR in IMT
Phase 1: assess the MTD/RP2D regimen
Phase 1: to characterize the PK of brigatinib
Phase 2: EFS in ALCL
(ICTRP)

non disponible

Date d'enregistrement
17.05.2021 (ICTRP)

Inclusion du premier participant
18.08.2022 (ICTRP)

Sponsors secondaires
Takeda
(ICTRP)

Contacts supplémentaires
Michel Zwaan, Prof, Princess Maxima Center for Pediatric Oncology in The Netherlands (ICTRP)

ID secondaires
ITCC-098 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04925609 (ICTRP)