Chronic Myelogenous Leukemia in chronic phase (CML-CP) in newly diagnosed patients MedDRA version: 21.0 Level: LLT Classification code 10009012 Term: Chronic myelogenous leukemia System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants eligible for inclusion in this study must meet all of the following criteria: 1. Male or female participants = 18 years of age. 2. Participants with CML-CP within 3 months of diagnosis. 3a. Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of the Philadelphia chromosome of (9;22) translocations (presence of BCR-ABL1 in a review of a minimum 20 metaphases is required). - Documented chronic phase CML will meet all the below criteria Hochhaus et al 2020: • ULN - = 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis 6a. Participants must have the following laboratory values within normal limits or corrected to within normal limits with supplements prior to randomization: • Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with CrCl* = 90 mL/min) • Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with CrCl* = 90 mL/min) • Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl* = 90 mL/min) • For participants with mild to moderate renal impairment (CrCl* = 30 mL/min and =65 years) yes F.1.3.1 Number of subjects for this age range 121
Exclusion criteria
Exclusion criteria: 1a.Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide. Treatment with either imatinib, or nilotinib, or dasatinib or bosutinib for =2 weeks is allowed.No treatment with other tyrosine kinase inhibitors prior to randomization is permitted. 2.Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required). 3.Impaired cardiac function or cardiac repolarization abnormality including but not limited to any one of the following: •History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) •Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) •QTc = 450 ms (male participants), =460 ms (female participants) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF = 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the participant re-screened for QTc. •Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: •Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia •Concomitant medication(s) with a “Known risk of Torsades de Pointes” per www.crediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication. •Inability to determine the QTcF interval 4.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 (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia). Please refer to Section 6.3.1 5.History of significant congenital or acquired bleeding disorder unrelated to cancer. 6.Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery. 7.History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively 8.History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis. 9.History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease. 10. Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the efficacy of asciminib versus Investigator selected TKI, with respect to proportion of participants in Major Molecular Response (MMR) at Week 48. 2. To compare the efficacy of asciminib versus Investigator selected TKI, within the stratum of participants with imatinib as the pre-randomization selected TKI, with respect to proportion of participants in MMR at Week 48. ;Secondary Objective: 1. To compare the efficacy of asciminib versus Investigator selected TKI, with respect to proportion of participants in MMR at Week 96. 2. To compare the efficacy of asciminib versus Investigator selected TKI, within the stratum of participants with imatinib as the pre-randomization selected TKI, with respect to proportion of participants in MMR at Week 96 3. To characterize the safety and tolerability profile of asciminib versus 2G TKIs: nilotinib, dasatinib or bosutinib 4. Other protocol-defined secondary objectives will apply; please see the protocol for a detailed list of all secondary objectives ;Primary end point(s): Major Molecular response (MMR) at Week 48 (Yes/No) ;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Major Molecular response (MMR) at Week 96 (Yes/No) 2. Time to discontinuation of study treatment due to Adverse Events (TTDAE) 3. Other protocol-defined secondary endpoints will apply; please see protocol for a detailed list of all secondary endpoints;Timepoint(s) of evaluation of this end point: 1. 96 weeks 2. 96 weeks after last patient first dose 3. Other protocol-defined timepoints of evaluation will apply; please see protocol for a full list of timepoints for all endpoints | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, Czech Republic, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Norway, Portugal, Russian Federation, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States, Viet Nam
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed