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.

Novartis Pharmaceuticals130 个研究点分布在 8 个国家目标入组 568 人2022年11月21日

适应症Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

干预措施Asciminib Nilotinib

概览

阶段: 3 期
干预措施: Asciminib
疾病 / 适应症: Philadelphia Chromosome-Positive Chronic Myeloid Leukemia
发起方: Novartis Pharmaceuticals
入组人数: 568
试验地点: 130
主要终点: Time to discontinuation of study treatment due to adverse event (TTDAE).
状态: 进行中（未招募）
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

The primary purpose of this study was to assess the tolerability of oral asciminib (80 mg QD) in comparison with that of the second generation (2G) Tyrosine Kinase Inhibitor (TKI) nilotinib (300 mg BID), in adult patients with newly diagnosed Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).

详细描述

Participants were randomized in the study in a 1:1 ratio to asciminib or nilotinib. No crossover of study treatment across arms were allowed. Randomization was stratified based on European Treatment Outcome Study (EUTOS) long-term survival (ELTS) score (low versus intermediate versus high) to help achieve a balance between the treatment arms. The primary analysis was performed when approximately 65 discontinuations of either study treatment due to Adverse Event (AE) occured. Eligible participants on both arms could choose to participate in an optional 2-year Treatment Free Remission (TFR) Phase. Participants with loss of Major Molecular Response (MMR) during TFR Phase were to enter the Treatment Re-initiation (TRI) Phase.

注册库

clinicaltrials.gov

开始日期

2022年11月21日

结束日期

2031年7月7日

最后更新

2个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Novartis Pharmaceuticals

责任方

Sponsor

入排标准

入选标准

•Signed informed consent must be obtained prior to participation in the study.
•Male or female patients ≥ 18 years of age.
•Patients with CML-CP within 3 months of diagnosis.
•Diagnosis of CML-CP (European Leukemia Network \[ELN\] 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):
•\< 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.

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.
•Known cytopathologically confirmed central nervous system (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 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 atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block).
•QT interval corrected by Fridericia's formula (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.

研究组 & 干预措施

Asciminib

Participants received asciminib 80 mg once a day (QD).

干预措施: Asciminib

Nilotinib

Participants will receive nilotinib 300 mg BID

干预措施: Nilotinib

结局指标

主要结局

Time to discontinuation of study treatment due to adverse event (TTDAE).

时间窗: From date of first dose to date of treatment discontinuation due to AE, assessed up to 5 years

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).

次要结局

Percentage of participants with Major Molecular response (MMR) at scheduled data collection time points(approximately 7.5 years)
Percentage of participants with Major Molecular response (MMR) by scheduled data collection time points(approximately 7.5 years)
Percentage of participants with MR4.0 at scheduled data collection time points(approximately 7.5 years)
Percentage of participants with MR4.0 by scheduled data collection time points(approximately 7.5 years)
Percentage of participants with MR4.5 at scheduled data collection time points(approximately 7.5 years)
Percentage of participants with MR4.5 by scheduled data collection time points(approximately 7.5 years)
Percentage of participants with Complete Hematological response (CHR) at scheduled data collection time points(approximately 7.5 years)
Percentage of participants with Complete Hematological response (CHR) by scheduled data collection time points(approximately 7.5 years)
Percentage of participants with BCR::ABL1 ratio ≤1% at scheduled data collection time points(approximately 7.5 years)
Percentage of participants with BCR::ABL1 ratio ≤1% by scheduled data collection timepoints(approximately 7.5 years)
Duration of MMR(approximately 7.5 years)
Duration of MR4.0(approximately 7.5 years)
Duration of MR4.5(approximately 7.5 years)
Time to first MMR(approximately 7.5 years)
Time to first MR4.0(approximately 7.5 years)
Time to first MR4.5(approximately 7.5 years)
Time to treatment failure (TTF).(approximately 7.5 years)
Event free survival (EFS)(approximately 7.5 years)
Progression free survival (PFS).(approximately 7.5 years)
Overall survival (OS).(approximately 7.5 years)
Time to treatment discontinuation (TTD) due to selected reasons(approximately 7.5 years)
Change from baseline in overall scores and individual scales of the European organization for research and treatment of cancer - quality of life questionnaire (EORTC QLQ-C30)(approximately 7.5 years)
Change from baseline in overall scores and individual scales of the European organization for research and treatment of cancer CML module (EORTC QLQ-CML24)(approximately 7.5 years)