NCT04126681已完成2 期
A Phase 2, Randomized, Open Label, Pivotal Study to Evaluate the Efficacy and Safety of HQP1351 in CML CP Patients Who Are Resistant and/or Intolerant to First- and Second-Generation Tyrosine Kinase Inhibitors
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 22
- 主要终点
- Event free survival (EFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of HQP1351 in patients with chronic myeloid leukemia in chronic phase (CML-CP) who are resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors. The efficacy of HQP1351 is determined by evaluating the subjects' event free survival (EFS).
详细描述
This is a phase 2, randomized, open label, pivotal study to evaluate the efficacy and safety of HQP1351 in CML CP patients who are resistant and/or intolerant to first- and second-generation TKIs in China. A total of 141 CML CP patients will be included in this study. After screening, eligible subjects will be randomized by 2:1 ratio to enter HQP1351 therapy cohort and best available therapy (BAT) cohort. When the subjects in the two cohorts reach EFS assessment, they can crossover to contralateral cohort if the investigator and Sponsor think they could be clinically benefited. During treatment, each subject will be assessed regularly for hematological, cytogenetic and molecular responses. At the same time, safety information also will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-lactating female patients who are 18 years of age or older.
- •CML-CP patients with positive Ph chromosome or BCR-ABL fusion genes.
- •Resistance and intolerance of first- and second-generation TKIs: defined as resistance or intolerance to imatinib, nilotinib, and dasatinib.
- •Ability to understand and willingness to sign a written informed consent form. The consent form must be signed by the patient prior to any study specific procedures.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Predicted life expectancy of ≥3 months.
- •Organ function as indicated by the following laboratory indicators must be met (Hematological indicators require that no blood transfusion or any blood products or cytokines be used within 14 days prior to testing):
- •Hemoglobin ≥8.0g/dL.
- •White blood cell count ≥ 3.0×10^9/L.
- •Platelet count ≥ 75×10^9/L.
- •Serum creatinine ≤ 1.5×upper limit of normal (ULN) or 24 hours calculated creatinine clearance ≥ 50mL/min when serum creatinine >1.5×ULN.
- •Serum albumin ≥ 3.0 g/dL.
- •Total bilirubin ≤ 1.5 x ULN.
- •Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN.
- •Amylase≤1.5×ULN. Lipase≤1.5×ULN.
- •PT/APTT/INR≤1.5×ULN.
- •Cardiac function index: ejection fraction (EF) > 50%, pulmonary arterial systolic pressure (PASP) ≤50 mmHg.
- •QT interval corrected on electrocardiogram (ECG) evaluation: QTc≤450ms in males or ≤470ms in females.
- •Males and females of childbearing potential and their partners voluntarily take contraceptive measures that the researchers believe are effective within 120 days from the signing of the informed consent to the last use of the research drug, or confirm that sterilization has been performed (at least one month before screening).
- •Willingness and ability to comply with study procedures and follow-up examination.
排除标准
- •Received cytotoxic chemotherapy or radiotherapy within 28 days prior to the first administration, interferon or cytarabine or antitumor effect Chinese herbal medicine or Chinese patent medicine within 14 days prior to the first administration, or targeted BCR-ABL1 TKI within 7 days prior to the first administration, or hydroxyurea or anagrelide within 24 hours after the first administration, or adverse events (except alopecia) caused by previous treatment and have not recovered.
- •The patients who received any other investigating drugs within 14 days prior to first administration.
- •For patients with CML-CP, if they have progressed to AP or BP, they cannot be enrolled after treatment with CML-CP.
- •Patients who are currently receiving treatment with a medication that has the potential to interact with research drug.
- •Have previously been treated with ponatinib or HQP1351 (or drugs of similar composition).
- •Absorption disorder syndrome or other diseases affecting oral drug absorption.
- •Have any history of heart or vascular disease, such as hypertension (systolic blood pressure (HBP) > 140mmHg and/or diastolic blood pressure > 90mmHg), or take medications that are known to cause QT interval prolongation. The patients with well controlled HBP can be included.
- •Pulmonary systolic pressure (PSP) of echocardiography is more than 50 mmHg, or there is clinical symptom related to pulmonary hypertension.
- •Have a history of serious cardiovascular diseases during the previous treatment of chronic myeloid leukemia with TKI, including myocardial infarction, unstable angina pectoris, severe arrhythmia and congestive heart failure.
- •Underwent autologous or allogeneic stem cell transplant.
- •CML-CP patient currently diagnosed as Complete cytogenetic response (CCyR).
- •Have diseases with abnormal bleeding and coagulation function, or have a bleeding disorder unrelated to CML within 3 months before first dose of study drug.
- •Underwent major surgery (except minor surgical procedures, such as placement or bone marrow biopsy) with 14 days prior to the first dose of study drug.
- •Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy (It is defined as a daily dose of corticosteroids less than 30 mg prednisone or the same amount of other corticosteroids within 7 days).
- •Have active nervous system (CNS) disease as evidence by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required.
- •History of another primary malignancies.
- •Active symptomatic infection.
- •Known to be allergic to study drug ingredients or their analogues.
- •Female patients with blood β-Human chorionic gonadotropin positive, pregnant or lactating or expecting pregnancy during the study program.
- •Suffer from any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the research drug.
研究组 & 干预措施
HQP1351 therapy cohort
Experimental
HQP1351 40 mg, taken orally once every other day of a 28-day cycle
干预措施: HQP1351 (Drug)
Best Available Therapy (BAT) cohort
Active Comparator
Best available therapy (BAT) will be selected by the investigator for each participant.
干预措施: Hydroxyurea or Interferon-based therapy (Drug)
Best Available Therapy (BAT) cohort
Active Comparator
Best available therapy (BAT) will be selected by the investigator for each participant.
干预措施: Homoharringtonine (Drug)
Best Available Therapy (BAT) cohort
Active Comparator
Best available therapy (BAT) will be selected by the investigator for each participant.
干预措施: Imatinib, Dasatinib or Nilotinib (Drug)
结局指标
主要结局
Event free survival (EFS)
时间窗: By the end of Cycle 24 (each cycle is 28 days)
EFS is defined as any "event" occurred since randomization, such as disease progression.
次要结局
- Progression free survival (PFS)(By the end of Cycle 24 (each cycle is 28 days))
- Overall survive (OS)(By the end of Cycle 24 (each cycle is 28 days))
- Complete hematologic response (CHR)(By the end of Cycle 24 (each cycle is 28 days))
- Major cytogenetic response (MCyR)(By the end of Cycle 24 (each cycle is 28 days))
- Major molecular response (MMR)(By the end of Cycle 24 (each cycle is 28 days))
- Complete cytogenetic response (CCyR)(By the end of Cycle 24 (each cycle is 28 days))
- Incidence and severity of adverse events(By the end of Cycle 24 (each cycle is 28 days))
研究者
研究点 (22)
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