A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (=18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)
- Conditions
- Philadelphia Chromosome-Positive Chronic Myeloid LeukemiaCMLC92.1
- Registration Number
- LBCTR2023025267
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- All
- Target Recruitment
- 5
Inclusion Criteria:
1- Patients with CML-CP within 3 months of diagnosis.
2- Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of the Philadelphia chromosome
Documented chronic phase CML will meet all the below criteria Baccarani et al 2013:
< 15% blasts in peripheral blood and bone marrow,
< 30% blasts plus promyelocytes in peripheral blood and bone marrow,
< 20% basophils in the peripheral blood,
PLT count = 100 x 10^9/L (= 100,000/mm3), except treatment induced thrombocytopenia
No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
3- Evidence of typical BCR::ABL1 transcript [e14a2 and/or e13a2] which is amenable to standardized RQ-PCR quantification by the central laboratory assessment.
4- ECOG performance status of 0 or 1.
5- Adequate end organ function as defined by:
Total bilirubin (TBL) < 3 x ULN; patients with Gilbert's syndrome may only be included if TBL = 3.0 x ULN or direct bilirubin = 1.5 x ULN,
CrCl = 30 mL/min as calculated using Cockcroft-Gault formula, Serum lipase = 1.5 x ULN. For serum lipase > ULN - = 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis.
6- 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 <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be within normal limits or corrected to within normal limits with supplements prior to randomization.
CrCl as calculated using Cockcroft-Gault formula.
Other protocol-defined Inclusion/exclusion criteria will apply
Exclusion Criteria:
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 (male patients), =460 ms (female patients) 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 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 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 d
dose of anti-retroviral therapy at the time of screening.
Other protocol-defined Inclusion/exclusion criteria will apply
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ame: Time to discontinuation of study treatment due to adverse event (TTDAE);Timepoints: From date of first dose to date of treatment discontinuation due to AE, assessed up to 4.5 years ;Measure: 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)
- Secondary Outcome Measures
Name Time Method