Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia
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
Novartis Pharmaceuticals
44 participants
Dec 27, 2021
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria13
- \- 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 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 Criteria11
- Known presence of the T315I mutation prior to study entry or a BCR::ABL mutation with known resistance to study treatment any time 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.
Interventions
Asciminib Pediatric formulation group: 1 mg film-coated granules in a size 0 capsule will be supplied, taken orally (capsules are a container for the granules and are not ingested): 10 mg (10x 1 mg film-coated granules in capsule) 15 mg (15x 1 mg film-coated granules in capsule) 20 mg (20x 1 mg film-coated granules in capsule) 30 mg (30x 1 mg film-coated granules in capsule)
Asciminib Adult formulation group: 40 mg tablets BID, taken orally. 20 mg tablets BID, taken orally.
Locations(40)
View Full Details on ClinicalTrials.gov
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NCT04925479