2023-508838-33-00招募中3 期
A phase III, multi-center, open-label, randomized study of oral asciminib versus Investigator selected TKI in patients with newly diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 159
- 试验地点
- 41
- 主要终点
- Major Molecular Response (MMR) at Week 48 (Yes/No)
研究概览
简要总结
To compare the efficacy of asciminib versus Investigator selected TKI with respect to the proportion of participants that are in Major Molecular Response (MMR) at Week 48. 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 the proportion of participants that are in MMR at Week 48.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female participants ≥ 18 years of age.
- •Participants 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 (Hochhaus et al 2020): • < 15% blasts in peripheral blood and bone marrow, • < 30% blasts plus promyelocytes in peripheral blood and bone marrow, • < 20% basophils in the peripheral blood, • Platelet (PLT) count ≥ 100 x 109/L (≥ 100,000/mm3), • No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate end organ function as defined by: • Total bilirubin (TBL) < 3 x upper limit of normal (ULN); participants with Gilbert’s syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN • Creatinine clearance (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
- •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 <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be ≥ LLN or corrected to within normal limits with supplements prior to randomization. • CrCl* as calculated using Cockcroft-Gault formula
- •Signed informed consent must be obtained prior to any study related screening procedures being performed.
- •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.
排除标准
- •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.
- •Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
- •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 //.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.
- •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).
- •History of significant congenital or acquired bleeding disorder unrelated to cancer.
- •Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery.
- •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.
- •History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
- •History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.
结局指标
主要结局
Major Molecular Response (MMR) at Week 48 (Yes/No)
Major Molecular Response (MMR) at Week 48 (Yes/No)
次要结局
- Major Molecular Response (MMR) at Week 96 (Yes/No)
- Major Molecular response (MMR) at Week 96 (Yes/No)
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (41)
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