A Phase IIIb, Multi-center, Open-label, Randomized Study of Tolerability and Efficacy of Oral Asciminib Versus Nilotinib in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase.
The study is designed to compare the tolerability of asciminib versus nilotinib for the treatment of newly diagnosed, previously untreated patients with Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).
• Patients with CML-CP within 3 months of diagnosis.
• 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.
• Evidence of typical BCR::ABL1 transcript [e14a2 and/or e13a2] which is amenable to standardized RQ-PCR quantification by the central laboratory assessment.
• ECOG performance status of 0 or 1.
• 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.
• 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.