A Multi-center, Open-label Study to Determine the Dose and Safety of Oral Asciminib in Pediatric Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP), Previously Treated With One or More Tyrosine Kinase Inhibitors

  • STATUS
    Recruiting
  • End date
    Jul 6, 2029
  • participants needed
    34
  • sponsor
    Novartis Pharmaceuticals
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Updated on 20 October 2022
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leukemia
basophils
asciminib

Summary

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.

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 follow a two-part study design consisting of a dose determination part (Part 1) and a cohort expansion (Part 2).

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 remaining patients will be enrolled in Part 2 until at least 30 participants, including those who were included in Part 1, have been enrolled (15 per age group) in the pediatric formulation group.

Due to the fact that the pediatric formulation is currently in development and not yet available, this study will start with the recruitment of adolescent patients. These participants aged 14 to <18 years, weighing at least 40 kg will 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 is planned after all participants have completed at least 52 weeks of study treatment or discontinued earlier.

Details
Condition Myeloid Leukemia, Philadelphia Positive
Treatment Asciminib Pediatric formulation group, Asciminib Adult formulation group
Clinical Study IdentifierNCT04925479
SponsorNovartis Pharmaceuticals
Last Modified on20 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Male or female participants: Pediatric formulation group: ≥ 1 and less than 18 years of age at study entry. Adult formulation group: ≥ 14 and less than 18 years of age and body weight of ≥ 40 kg at study entry
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
< 15% blasts in peripheral blood and bone marrow
< 30% combined blasts plus promyelocytes in peripheral blood and bone marrow
< 20% basophils in the peripheral blood
Neutrophils ≥ 1.5 x 10^9/L (or WBC ≥ 3 x 10^9/L if neutrophils are not available) and platelet count ≥ 100 x 10^9/L
No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
Prior treatment with a minimum of one TKI
Failure (adapted from the 2020 European Leukemia Net (ELN) Guidelines Hochhaus et al 2020) 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

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
Severe and/or uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol
History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
History of acute or chronic liver disease
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
Pregnant or nursing (lactating) females
Other protocol-defined inclusion/exclusion may apply
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