Health Condition 1: C921- Chronic myeloid leukemia, BCR/ABL-positive
Conditions
Interventions
Intervention1: Asciminib: 80 mg BID or 200mg BID orally daily, for 6 months.
Control Intervention1: NIL: NIL
Sponsors
Novartis Healthcare Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Confirmed diagnosis of Ph+ CML-CP. 2. Laboratory values as confirmed by the available reports of the peripheral blood test or bone marrow examination (performed within 12 months before the screening) at the screening visit to meet the criteria of Ph+ CML-CP: a) More than 15% blasts in peripheral blood and/or bone marrow b) More than 30% blasts plus promyelocytes in peripheral blood and/or bone marrow c) More than 20% basophils in the peripheral blood d) More than and equal to 50 x 109/L (>=50,000/mm3) platelets e) No evidence of extramedullary leukemic involvement, apart from hepatosplenomegaly 3. For Ph+ CML-CP participants with T315I mutation, mutational analysis testing at any time point showing a documented T315I mutation. For Ph+ CML-CP participants without T315I mutation, at least 2 prior adenosine triphosphate (ATP)-site TKIs (i.e., imatinib, nilotinib, bosutinib, dasatinib, or ponatinib) with failure (adapted from the 2020 European Leukemia Net [ELN] Recommendations) or intolerance to the most recent TKI therapy at the time of screening. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 5. Evidence of typical BCR/ABL1 transcript (e14a2 and or e13a2) at the time of screening which is amenable to standardized RQ-PCR quantification. 6. Participants must have adequate end organ function as per the investigatorâ??s judgement. 7. Participants must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to the first dose of study treatment: a. Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits). b. Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dL or 3.1 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits). c. Magnesium, except for magnesium increase more than upper level of normal (ULN) â?? 3.0 mg/dL or more than ULN â?? 1.23 mmol/L associated with creatinine clearance (calculated using Cockcroft-Gault formula) within normal limits.
Exclusion criteria
Exclusion criteria: 1. Known second chronic phase of CML after previous progression to CML-acute phase (AP)/CML-blast crisis (BC). 2. Previous treatment with a hematopoietic stem-cell transplantation. 3. Cardiac or cardiac repolarization abnormality, including any of the following: a. History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, and coronary artery bypass graft (CABG) b. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block) c. QT corrected for heart rate by Fridericiaâ??s cube root formula (QTcF) at screening >=450 msec (both male and female participants) d. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i) Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. ii) Inability to determine the QTcF interval. 4. Concomitant medication(s) with a â??Known risk of TdP ? (per www.crediblemeds.org/) that cannot be discontinued or replaced 7 days prior to starting study treatment by safe alternative medication. 5. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis. 6. Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C. 7. Known presence of significant congenital or acquired bleeding disorder unrelated to cancer. 8. Previous treatment with or known/suspected hypersensitivity to asciminib or any of its excipients. 9. Participants must avoid consumption of grapefruit, Seville oranges, or products containing the juice of each during the entire study and 7 days before the first dose of study treatment, due to potential CYP3A4 interaction with the study treatment. Orange juice is allowed. Participants must avoid consumption of over-the-counter medications or herbal supplements as these can interact with each other and may alter the effects of asciminib. 10. Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer. 11. Pregnant or breastfeeding women. 12. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception. 13. If a participant is presenting with symptoms suggestive of possible Coronavirus Disease (COVID-19) infection, advise ruling it out by appropriate testing recommended by health authorities. 14. Nucleic acid amplification tests for viral RNA (polymerase chain reaction), to measure current infection with SARS-CoV-2 15. Antigen tests for rapid detection of SARS-CoV-2 16. Antibody (serology) tests to detect the presence of antibodies to SARS-CoV-2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Frequency and severity of adverse events (AEs)/serious AEs (SAEs) in participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more TKIs up to 6 months 2. Frequency and severity of AEs/SAEs in participants with Ph+ CML-CP with T315I mutationTimepoint: upto 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Ph+ CML-CP Previously treated with 2 or more TKIâ??s (without T3151 mutation) 1. Proportion of participants with dose interruptions, reductions, & discontinuation up to 6 months 2. Percentage of participants achieving a complete hematologic response (CHR) at 3 & 6 months of the treatment period 3. Percentage of participants achieving early molecular response (EMR), molecular response (MR2), major molecular response (MMR), & molecular response of MR4 & MR4.5 at 3 & 6 months of the treatment period 4. Time to achieve CHR, EMR, MR2, MMR, MR4, & MR4.5 during the treatment periodTimepoint: During 6 months of the treatment period;Ph+ CML-CP with T3151 mutation 1. Proportion of participants with dose interruptions, reductions, & discontinuation up to 6 months 2. Percentage of participants achieving a CHR at 3 & 6 months of the treatment period 3. Percentage of participants achieving EMR, MR2, MMR, MR4, & MR4.5 at 3 & 6 months of the treatment period 4. Time to achieve CHR, EMR, MR2, MMR, MR4, & MR4.5 during the treatment period 5. Duration of CHR, EMR, MR2, MMR, MR4, & MR4.5 during the treatment periodTimepoint: During the 6 months treatment period | — |
Countries
India
Contacts
Public ContactDr Chetan Metha
Novartis Healthcare Private Limited
Outcome results
None listed