Philadelphia Chromosome-Positive 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: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Male or female patients = 18 years of age. 3. Patients with CML-CP within 3 months of diagnosis. 4. Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of the Philadelphia (Ph) chromosome. A cryptic Ph chromosome should be confirmed by metaphase Fluorescence In Situ Hybridization (FISH). • Documented chronic phase CML will meet all the below criteria (Baccarani et al 2013): • ULN - = 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis. 8. Patients 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 patients 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 49
Exclusion criteria
Exclusion criteria: Participants meeting any of the following criteria are not eligible for inclusion in this study. 1. 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. 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 of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment. • 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). • QTcF = 450 ms on the average of three serial baseline ECG (using the QTcF formula). If QTcF = 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTcF. • 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 crediblemeds.org that cannot be discontinued or replaced 7 days prior to starting study treatment 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). 5. History of significant congenital or acquired bleeding disorder unrelated to cancer. 6. Major surgery within 4 weeks prior to study entry or patients 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. Known history of chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab/anti HBc) will be performed at screening. If anti-HBc is positive, HBV-DNA evaluation will be carried out at screening. A patient having positive HBV-DNA will not be enrolled in the study. Also, a patient with positive HBsAg will not be enrolled in the study. HCV Ab testing will also be performed at screening. For details on the criteria see Appendix 4. 11. History of Human Immunodeficiency Virus (HIV) unless well-controlled on a stable dose of anti-retroviral therapy at the time of screening. 12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study treatment (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To compare the efficacy of asciminib versus nilotinib at and by all scheduled data collection time points -Time to Treatment Discontinuation (TTD) forselected reasons of discontinuation -To assess the effect of asciminib versus nilotinib on patient-reported disease-related symptoms, functioning, and health-related quality of life (HRQoL). -To characterize the safety and tolerability profile of asciminib versus nilotinib during the course of study. ;Primary end point(s): -Time to discontinuation of study treatment due to adverse event (TTDAE). TTDAE is defined as the time from the date of first dose of study treatment to the date of discontinuation of study treatment due to adverse event (AE) ;Timepoint(s) of evaluation of this end point: From date of first dose to date of treatment discontinuation due to AE, assessed up to 4.5 years;Main Objective: The primary objective of the study is to assess the tolerability of asciminib versus nilotinib, in participants with newly diagnosed CML-CP, with respect to the time to discontinuation of study treatment due to adverse event (TTDAE). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • MMR at all scheduled data collection time points. • MMR by all scheduled data collection time points. • MR4.0 and MR4.5 at and by all scheduled data collection time points. • Complete Hematological Response (CHR) at and by all scheduled data collection time points. • BCR: ABL1 =1% at and by all data collection time points. • Duration of MMR, MR4.0, MR4.5. • Time to first* MMR, first MR4.0, first MR4.5. • Time to treatment failure. • Event Free Survival. • Progression free survival. • Overall survival. • TTD due to selected reasons (i.e. Discontinuation due to lack of efficacy/treatment failure/disease progression/ suboptimal response/death) • Change from baseline in overall scores and individual scales of the EORTC QLQ-C30, EORTC QLQ-CML24. • Type, frequency and severity of adverse events, dose modification due to adverse event, changes in laboratory values that fall outside the pre-determined ranges and clinically notable ECG changes, and other safety data (vital signs, physical examination). *by competing risk analysis;Timepoint(s) of evaluation of this end point: Up to 4.5 years | — |
Countries
Argentina, Bulgaria, Canada, Czechia, Czech Republic, France, Germany, Greece, Hungary, India, Ireland, Italy, Jordan, Korea, Republic of, Lebanon, Malaysia, Netherlands, Norway, Oman, Romania, Singapore, Slovakia, South Africa, Sweden, Switzerland, Türkiye, United Arab Emirates, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed