2024-511495-32-00招募中3 期
A Global Multicenter, Open Label, Randomized, Phase 3 Registrational Study of Olverembatinib (HQP1351) in Patients with Chronic Phase Chronic Myeloid Leukemia (POLARIS-2)
Ascentage Pharma Group Inc., Ascentage Pharma Group Inc.45 个研究点 分布在 6 个国家目标入组 138 人开始时间: 2025年1月20日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 138
- 试验地点
- 45
- 主要终点
- Part A: MMR rate at 24 weeks
研究概览
简要总结
Part A: To compare the major molecular response (MMR) rate at 24 weeks of olverembatinib versus bosutinib Part B: To evaluate the MMR rate by 24 weeks of olverembatinib in CML-CP patients with T315I mutation
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Part B
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old.
- •Adequate organ functions as defined below: • Creatinine clearance ≥30 mL/min as calculated using Cockcroft-Gault formula. • Total bilirubin < 1.5 × ULN except for patients with Gilbert’s syndrome who may only be included if total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5× ULN. • AST < 3 × ULN • ALT < 3 × ULN • Serum amylase ≤ 1.5 × ULN. For serum lipase ≤ 1.0 × ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis • Alkaline phosphatase ≤ 2.5 × ULN
- •Must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication: • Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits) • Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits)Magnesium, except for magnesium increase > ULN – 3.0 mg/dL; > ULN – 1.23 mmol/L associated with creatinine clearance (calculated using Cockcroft-Gault formula) within normal limits
- •Diagnosis of CML-CP according to CML NCCN Guidelines version 1.2024
- •Evidence of typical BCR::ABL1 transcript at the timing of screening which are amenable to standardized RQ-PCR quantification.
- •Must meet all the following laboratory values at the screening visit: • Peripheral blood myeloblasts < 15% • Peripheral blood myeloblasts and promyelocytes combined < 30% • Peripheral blood basophils < 20% • ≥ 50 × 109/L (≥ 50,000/mm3) platelets • Transient prior therapy related thrombocytopenia (<50,000/mm3 for ≤ 30 days prior to screening) is acceptable. • No evidence of extramedullary infiltrates of leukemia cells, except for hepatomegaly or splenomegaly
- •Part A: Prior treated with at least two approved TKIs, such as imatinib, nilotinib, dasatinib, radotinib, flumatinib, ponatinib, or asciminib
- •Part B: Patients must meet all three of the following criteria at screening. • Previously treated with at least one approved TKIs, such as imatinib, nilotinib, dasatinib, bosutinib, radotinib, flumatinib, ponatinib, or asciminib. • Have T315I mutation at screening. • There are no other effective and/or tolerable therapies available
- •Failure (adapted from the 2013 ELN Guidelines; Baccarani et al 2013) or intolerance to the most recent TKI therapy at the time of screening. • Failure is defined for CML-CP patients (CP at the time of initiation of last therapy) as follows. Patients must meet at least one of the following criteria. Three months after the initiation of therapy: No CHR or >95% Ph+ metaphases Six months after the initiation of therapy: BCR::ABL1 (IS) >10% and/or >65% Ph+ metaphases Twelve months after initiation of therapy: BCR::ABL1 (IS) >10% and/or >35% Ph+ metaphases At any time after the initiation of therapy, loss of CHR, CCyR or PCyR At any time after the initiation of therapy, the development of new BCR::ABL1 mutations which potentially cause resistance to current treatment At any time after the initiation of therapy, confirmed loss of MMR in 2 consecutive tests, of which one must have a BCR::ABL1 (IS) ≥1% At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: CCA/Ph+ • Intolerance is defined as below. Patients intolerant to the most recent TKI therapy must have BCR::ABL1 (IS) ratio more than 0.1% at screening. Non-hematological intolerance: patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal) Hematological intolerance: patients with grade 3 or 4 toxicity (ANC or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended in label.
- •ECOG performance status (PS) ≤
- •Written informed consent obtained prior to any screening procedures.
排除标准
- •For Part A only: T315I or V299L mutation at any time prior to starting study treatment.
- •Plan to undergo allogeneic hematopoietic stem cell transplantation
- •Clinically significant, uncontrolled, or active cardiovascular disease, specifically including any of the following prior to starting study treatment: • Any history of myocardial infarction (MI) within 6 months. • Unstable angina within 3 months. • Any history of cerebrovascular accident within 1 year. • Transient ischemic attacks (TIA) within 3 months. • Any history of peripheral vascular or visceral infarction within 6 months. • Congestive heart failure (CHF) (New York Heart Association [NYHA] class III or IV) within 6 months. • Left ventricular ejection fraction (LVEF) less than lower limit of normal, per local institutional standards, within 6 months History of clinically significant atrial arrhythmia (such as atrial fibrillation with increased risk of thrombosis) or any history of ventricular arrhythmia (determined by the treating physician). • Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 3 months prior to enrollment. Patients who have experienced a venous thromboembolic event should only be eligible if the condition is well controlled with optimal intervention (as determined by the treating physician). Continued prophylactic anticoagulation is acceptable. • Patients with revascularization procedures, including cardiac bypass within the 6 months and stenting within the past 3 months. • QTcF at screening ≥450 msec (male patients), ≥470 msec (female patients).
- •Presence of significant congenital or acquired bleeding disorder unrelated to CML
- •Another malignancy within 1 year of study entry. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry
- •Active infection that requires systemic drug therapy, including active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
- •For Part A only: patient with impairment of hepatic function, which is contraindicated in the bosutinib Summary of Product Characteristics.
- •Treatment with medications that meet one of the following criteria and cannot be discontinued at least 7 days prior to the first dose of olverembatinib or bosutinib. • Moderate or strong inhibitors of CYP3A4 • Moderate or strong inducers of CYP3A4
- •Previous treatment with or known / suspected hypersensitivity to olverembatinib or any of its excipients
- •For Part A only: Previous treatment with or known / suspected hypersensitivity to bosutinib or any of its excipients
- •Participation in an investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using adequate methods of contraception during dosing and for 4 months after last dose of olverembatinib and certain period according to the locally approved prescribing information for bosutinib.
- •Prior diagnosis of CML AP or BP
- •Previous treatment with hematopoietic stem-cell transplantation.
结局指标
主要结局
Part A: MMR rate at 24 weeks
Part A: MMR rate at 24 weeks
Part B: MMR rate by 24 weeks
Part B: MMR rate by 24 weeks
次要结局
- Part A: MMR rate at 96 weeks
- Part A: Cytogenetic response rate (complete, partial, major, minor, minimal, no response) at and by all scheduled data collection time points, including 24, 48 and 96 weeks
- Part A: MMR, MR4, MR4.5 rate at all scheduled data collection time points (except 24 and 96 weeks which are already covered by primary and key secondary endpoints)
- Part A: MMR, MR4, MR4.5 rate by all scheduled data collection time points including 24, 48 and 96 weeks
- Part A: Time to MMR, MR4, MR4.5
- Part A: Duration of MMR, MR4, MR4.5
- Part A: Time to complete cytogenetic response (CCyR)
- Part A: Duration of CCyR
- Part A: Time to treatment failure
- Part A: Progression free survival
- Part A: OS
- Part A: Type, frequency, and severity of adverse events
- Part A:Changes in laboratory values that fall outside the normal ranges and clinically notable ECG and other safety data (vital signs, physical examination)
- Part A:Trough plasma concentration; key PK parameters including apparent clearance, apparent volume of distribution and other appropriate parameters
- Part A: Change in health utility from baseline over time according to EQ-5D-5L
- Part A: Change in work productivity and activity impairment over time according to EORTC QLQ-C30
- Part B: MMR rate by 96 weeks
- Part B:Cytogenetic response rate (complete, partial, major, minor, minimal, no response) by all scheduled data collection time points, including 24, 48 and 96 weeks
- Part B:MMR, MR4, MR4.5 rate by all scheduled data collection time points (except 24 and 96 weeks, which are already covered by primary and key secondary endpoints)
- Part B:Time to MMR, MR4, MR4.5
- Part B:Duration of MMR, MR4, MR4.5
- Part B:Time to CCyR
- Part B:Duration of CCyR
- Part B: Time to treatment failure
- Part B:Progression free survival
- Part B:OS
- Part B:Type, frequency, and severity of adverse events.
- Part B:Changes in laboratory values that fall outside the normal ranges and clinically notable ECG and other safety data (vital signs, physical examination)
- Part B:Trough plasma concentration; key PK parameters including apparent clearance, apparent volume of distribution and other appropriate parameters
- Part B:Change in health utility from baseline over time according to EQ-5D-5L
- Part B:Change in work productivity and activity impairment over time according to EORTC QLQC30
研究者
Yifan Zhai, M.D., Ph.D.
Scientific
Ascentage Pharma Group Inc.
研究点 (45)
Loading locations...
相似试验
招募中
2 期
A study to learn more about how well treatment with sevabertinib (BAY2927088) tablets works and how safe it is in participants who have a solid tumor with mutations of the human epidermal growth factor receptor 2 (HER2)2024-517419-62-00Bayer Consumer Care AG, Bayer AG37
招募中
2 期
Orelabrutinib Plus Lisaftoclax and Rituximab in Untreated Mantle Cell Lymphoma With High-Risk DiseaseNCT07272499Ruijin Hospital25
招募中
2 期
Pembrolizumab + Lenvatinib for First Line Non-Clear Cell, Renal Cell Carcinoma2023-504944-32-00Merck Sharp & Dohme LLC59
招募中
2 期
Phase 2, Multicenter, Open label, Platform Study investigating Tarlatamab (AMG 757) in patients with Metastatic/Locally Advanced Small-Cell Lung Cancer (SCLC) and Other Poorly Differentiated Neuroendocrine Carcinomas (NECs), with biomarker analysis to characterize response/resistance (UNLOCK TARLATAMAB)2024-515847-47-00Institut Gustave Roussy30
招募中
2 期
Evaluation study of a treatement with Nivolumab and Ipilimumab or tKi according to molecular group in naïve metastatic Kidney cancer2024-520045-23-00ARTIC200