Study to determine the dose and safety of asciminib in pediatric patients with chronic myeloid leukemia

Phase 1

• Conditions: Pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), previously treated with one or more tyrosine kinase inhibitors; MedDRA version: 21.0Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10060498Term: Juvenile chronic myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 24.0Level: LLTClassification code 10082178Term: Philadelphia positive chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001286-20-IT
• Lead Sponsor: OVARTIS PHARMA AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-21
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Male or female participants:
a. Pediatric formulation group: =1 and less than 18 years of age at study entry.
b. Adult formulation group: =14 and less than 18 years of age and body weight of = 40 kg at study entry.
• Participants 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.
a. 15% blasts in peripheral blood and bone marrow
b. < 30% combined blasts plus promyelocytes in peripheral blood and bone marrow
c. < 20% basophils in the peripheral blood
d. Neutrophils = 1.5 x 10^9/L (or white blood cell (WBC) = 3 x 10^9/L if neutrophils are not available) and platelet count = 100 x 10^9/L
e. No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Prior treatment with a minimum of one TKI.
• Failure or intolerance to the most recent TKI therapy at the time of screening.
• Evidence of typical BCR-ABL fusion gene (BCR-ABL1) transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized real time quantitative polymerase chain reaction (RQ-PCR) quantification.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Known presence of the T315I mutation prior to study entry.
• Known second chronic phase of CML after previous progression to AP/BC.
• Previous treatment with a hematopoietic stem-cell transplantation.
• Patient planning to undergo allogeneic hematopoietic stem cell transplantation.
• Cardiac or cardiac repolarization abnormality.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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).;Secondary Objective: •To assess the safety and tolerability of asciminib.<br>•To assess pharmacodynamic markers of asciminib's anti-leukemic activity.<br>•To assess acceptability and palatability of the pediatric formulation.<br>•To assess long-term safety of asciminib.;Primary end point(s): • Primary PK parameters of asciminib: AUClast, AUCtau<br>• Secondary PK parameters of asciminib: Cmax, Tmax, Ctrough.;Timepoint(s) of evaluation of this end point: Primary analysis after last patient has completed week 52 visit

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Number, seriousness, severity, and causality assessments of treatment-emergent adverse events and other safety data as considered appropriate.<br>• Activity: Hematologic and molecular responses.<br>• Questionnaire on acceptability and palatability after first dose, 4 and 52 weeks.<br>• Number, seriousness, severity, and causality assessments of treatment-emergent adverse events and other safety data as considered appropriate including growth and sexual maturation assessments.;Timepoint(s) of evaluation of this end point: Final analysis after last patient completes week 260 visit