newly diagnosed Ph+ CML-CP
Conditions
Interventions
Arm1: Asciminib 80 mg QD under fasting conditions
Arm2: Investigator selected TKI that will include one of the below treatments as per the pre-randomized selection of TKI (imatinib or the 2G TKI (nilo
Sponsors
Kazuyuki Suzuki
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 patients >= 18 years of age. 2. Patients with CML-CP within 3 months of diagnosis. 3. Diagnosis of CML-CP with cytogenetic confirmation of 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: - = 100 x 109/L (>=100,000/mm3), - No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1. 5. Adequate end organ function as defined by: - Total bilirubin (TBL) = 30 mL/min as calculated using Cockcroft-Gault formula - Serum lipase = ULN - == lower limit of normal (LLN) 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 ClCr* >= 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 ClCr* >= 90 mL/min) - Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with ClCr* >= 90 mL/min) - For patients with mild to moderate renal impairment (ClCr* >= 30 mL/min and = LLN or corrected to within normal limits with supplements prior to randomization. ClCr* as calculated using Cockcroft-Gault formula 7. Signed informed consent must be obtained prior to any study related screening procedures being performed. 8. Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which is amenable to standardized Real time quantitative polymerase chain reaction (RQ-PCR) quantification.
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. Treatment with imatinib for == 450 msec (male patients), >=460 msec (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF >= 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient 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). 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. 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. A patient having positive HBV-DNA should not be enrolled in the study. 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 drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the efficacy of asciminib versus Investigator selected TKI with respect to the proportion of patients that are in Major Molecular Response (MMR) at Week 48. To compare the efficacy of asciminib versus Investigator selected TKI, within the stratum of patients with imatinib as the pre-randomization selected TKI, with respect to the proportion of patients that are in MMR at Week 48 | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Malaysia, Netherlands, Norway, Portugal, Russia, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States, Vietnam
Contacts
Public ContactSuzuki Kazuyuki
Novartis Pharma. K.K.
Outcome results
None listed