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
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
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.
Myeloid Leukemia, Philadelphia Positive
Dec 27, 2021
Jul 06, 2029
1 Years - 18 Years (Child, Adult)
Asciminib Pediatric formulation group
Asciminib Pediatric formulation group: Mini-tablets will be supplied as size 0 capsules containing 1 mg mini-tablets, taken orally:
10 mg (10x 1 mg tablets in capsule) BID 15 mg (15x 1 mg tablets in capsule) 20 mg (20x 1 mg tablets in capsule) BID 30 mg (30x 1 mg tablets in capsule) BID
Asciminib Adult formulation group
Asciminib Adult formulation group:
40 mg tablets BID, taken orally. 20 mg tablets BID, taken orally.
- 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.
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.