2024-512696-12-00招募中2 期
Asciminib as single agent or in combination with nilotinib in the 1st-line treatment of BCR-ABL1+ Chronic Myeloid Leukemia: a GIMEMA-GELMC phase II study. CML1624
Fondazione Gimema Franco Mandelli Onlus, Grupo Espanol De Leucemia Mieloide Cronica (GELMC)42 个研究点 分布在 2 个国家目标入组 160 人开始时间: 2025年4月22日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 42
- 主要终点
- The primary endpoint is the rate of deep molecular response (MR4) at 2 years; patients with not evaluable molecular analysis may repeat a QPCR analysis in 1 month (25 months from day 1)
研究概览
简要总结
The primary objective is to assess the efficacy, in terms of achievement of DMR (MR4), of asciminib singleagent or in combination with nilotinib in the first-line treatment of patients with BCR::ABL1+ CML in early CP.
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
- •Cytogenetic and molecular confirmed diagnosis of Ph+ and BCR::ABL1+ CML
- •Age ≥ 18 years
- •Early chronic phase, less than 3 months from diagnosis
- •Evidence at the time of study entry of typical BCR::ABL1 RNA transcripts e13a2 or e14a2 (b2a2 or b3a2), which are required for BCR::ABL international scale reporting
- •Prior treatment with any TKI for 30 days or less; prior treatment with hydroxyurea or anagrelide is allowed
- •ECOG performance status of 0, 1 or 2
- •Adequate end organ function as defined by -Total bilirubin ≤ 1.5 x ULN except for patients with Gilbert’s syndrome who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN - Aspartate transaminase (AST) ≤ 3.0 x ULN- Alanine transaminase (ALT) ≤ 3.0 x ULN - Serum amylase ≤ 1.5 x ULN - Serum lipase ≤ 1.5 x ULN - Alkaline phosphatase ≤ 2.5 x ULN, unless considered tumor related - Creatinine clearance > 50 ml/min using Cockcroft-Gault formula
- •Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedure
- •An effective form of contraception with their sexual partners from enrolment through 30 days after the end of treatment.
排除标准
- •CML in blast phase (BP) or in second chronic phase after previous BP, according to WHO criteria
- •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, small bowel resection, or gastric bypass surgery)
- •Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- •Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after the end of treatment.
- •Previous treatment with TKIs for more than 30 days
- •Refusal or impossibility to give an informed consent
- •History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: recent myocardial infarction (within last 6 months), uncontrolled congestive heart failure, unstable angina (within last 6 months), clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
- •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)
- •History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- •History of acute or chronic liver disease
- •History of other active malignancy within 2 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
- •Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or 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 study entry
结局指标
主要结局
The primary endpoint is the rate of deep molecular response (MR4) at 2 years; patients with not evaluable molecular analysis may repeat a QPCR analysis in 1 month (25 months from day 1)
The primary endpoint is the rate of deep molecular response (MR4) at 2 years; patients with not evaluable molecular analysis may repeat a QPCR analysis in 1 month (25 months from day 1)
次要结局
- The rate of sustained MR4 or MR4.5 at 4 years (TFR eligibility) and the proportion of patients free from relapse (BCR::ABL1 transcript < 0.1%) 12 months after treatment discontinuation
- The rate of major molecular response (MR3) at and by 1, 2, 3, 6, 12, 18 and 24 months, and the rate of MR4 and MR4.5 at and by 1, 2, 3, 4 years
- The median time to response (MR3, MR4, MR4.5) and the relationship between the time to response (response at milestones) and the TFR eligibility at 4 years and the TFR rate 12 months after discontinuation
- Outcome measures at 2 and 5 years: overall survival (OS), survival without leukemia-related death, progression-free survival (PFS)
- Outcome measures at 5 years according to baseline prognostic factors (Sokal and ELTS score, CCA in Ph+ cells, BCR::ABL transcript type, and according to the early response (BCR::ABL transcript level at 3 and 6 months)
- Incidence and VAF of treatment emergent BCR::ABL1 mutations
- Incidence and VAF of BL and treatment emergent cancer related somatic mutations and relationship with treatment efficacy, including treatment-free remission and outcome
- Incidence of hematologic and non-hematologic adverse events
- Mean HRQoL scores trajectories by the EORTC QLQ-C30 and QLQ-CML24 questionnaires according to treatment arm
研究者
Data center
Scientific
Fondazione Gimema Franco Mandelli Onlus
研究点 (42)
Loading locations...
相似试验
招募中
2 期
Frontline Asciminib combination in chronic phase CML2024-516212-24-00Friedrich-Schiller-Universitaet Jena125
进行中（未招募）
3 期
在已完成诺华申办的 asciminib 研究且经研究者判断继续治疗可能获益的患者中评估长期安全性的研究CTR2024137126
招募中
2 期
Study to determine the dose and safety of asciminib in pediatric patients with chronic myeloid leukemia.2023-508129-28-00Novartis Pharma AG17
招募中
4 期
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels (ADAPT ALEC)2023-506886-76-00Universitair Medisch Centrum Groningen196
招募中
3 期
A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP2023-508838-33-00Novartis Pharma AG159