Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) previously treated with one or more TKIs. Full extrapolation of the efficacy of asciminib from adult to pediatric patients will be conducted. Full extrapolation is based on the concept that CML in the pediatric population has the same pathogenesis, similar clinical characteristics and progression pattern as in adults.
Full description
The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (PH+ CML-CP) previously treated with one or more Tyrosine kinase inhibitor (TKIs).
The primary objective of this study is to characterize the pharmacokinetic (PK) profile of asciminib in pediatric patients with the goal of identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
The pediatric formulation group will include at least 15 participants in each of the following two age categories: 1 to <12 years and 12 to <18 years; leading to at least 30 participants enrolled treated with the pediatric formulation. It will consist of a dose determination part (Part 1) and a cohort expansion (Part 2 BID regimen and Part 3 QD regimen).
In Part 1, 4-6 participants will be enrolled in order to obtain at least 4 participants evaluable for PK (these participants may be from either of the age categories described above). The initial starting dose will be based on body weight and will be administered BID with food.
Once the body weight adjusted dose has been determined in Part 1 of the study, the patients will be enrolled in Part 2 until at least 20 participants, including those who were included in Part 1, have been enrolled (10 per age group) in the pediatric formulation group. Once the interim safety and PK analysis 2 is completed for one of the age groups, the Part 3 QD regimen will open for the respective age group to enroll 10 patients (5 patients by age group).
Due to the fact that the pediatric formulation was in development and was not available, this study started with the recruitment of adolescent patients. These participants aged 14 to <18 years, weighing at least 40 kg receive the adult formulation at a flat dose of 40 mg BID under fasted conditions.
The total duration of the treatment period of the study will be 5 years (260 weeks). Participants who, according to Investigator's judgement, are benefiting from study treatment will remain on treatment up to the completion of the treatment period (Week 260/5 years). The primary analysis for the BID regimen is planned after all participants in Part 1 and 2 have completed at least 52 weeks of study treatment or discontinued earlier.
The primary analysis for combined regimen (BID+QD) is planned after all participants in Part 1, 2 and 3 have completed at least 52 weeks of study treatment or discontinued earlier.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Participants with Ph+ CML-CP must meet all of the following laboratory values at the screening visit. In the case where bone marrow blast and promyelocyte counts are available, these will be accepted if done within 56 days prior to the screening visit, to avoid unnecessary repetition of this test.
Prior treatment with a minimum of one TKI
Failure (adapted from the 2020 European Leukemia Net (ELN) Guidelines Hochhaus et al 2020 and 2013 ELN Guidelines Baccarani et al 2013) or intolerance to the most recent TKI therapy at the time of screening.
Performance status: Karnofsky ≥ 50% for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age at the time of screening
Participants must have adequate renal, hepatic, pancreatic and cardiac function
Participants must have electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:
Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized RQ-PCR quantification.
Exclusion criteria
Other protocol-defined inclusion/exclusion may apply.
Primary purpose
Allocation
Interventional model
Masking
34 participants in 1 patient group
There are currently no registered sites for this trial.
Central trial contact
Novartis Pharmaceuticals; Novartis Pharmaceuticals
Start date
Dec 27, 2021 • 3 years ago
Today
Dec 30, 2024
End date
Jun 30, 2026 • in 1 year and 5 months
Lead Sponsor
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal