A Phase 1 Clinical Study on the Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of QLF32101 in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity(DLT)
研究概览
简要总结
This study aimed to evaluate the safety,tolerability and preliminary efficacy of QLF32101 administered intravenously and subcutaneously in patients with R/R, AML.
详细描述
This open label, first-in-human study consists of 2 parts. Part 1 consists of dose escalation cohorts and Part 2 is expansion cohort.
The study population will include adult AML patients with relapse or refractory disease. In addition, in Part 2 medium and high-risk MDS patients are eligible.
In Part 1, dose escalations cohorts are followed until dose-limiting toxicity (DLT) or a maximum tolerated dose (MTD) or RecommendedPart2Dose (RP2D) is defined. Dose escalation decisions will be made by the Data Review Committee and will be primarily guided by safety data observed through the end of Cycle 1, as well as on-going assessment of safety beyond Cycle 1 in later cohorts.
Part 2 will begin once the MTD or RP2D is determined in Part 1. Part 2 will further characterize the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD), immunogenicity and to assess preliminary efficacy of QLF32101.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Gender unlimited, age ≥ 18 years old;
- •Volunteer to participate in clinical trials and sign informed consent;
- •AML and medium-high risk MDS patients confirmed by histology and cytology;
- •Estimated survival time is at least 12 weeks;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0~2;
- •Any adverse event related to previous anti-tumor treatment must have returned to ≤ grade 1(NCI-CTCAE v5.0);
- •Main organ function is basically normal;
- •All female and male patients with reproductive ability must agree to take effective contraceptive methods during the study and within 6 months after the last use of the trial drug,the blood pregnancy test of female patients of childbearing age must be negative within 7 days before the first use of the study drug.
排除标准
- •Previously received hematopoietic stem cell transplantation;
- •Previous exposure to any anti-CLL-1 monoclonal antibody or CAR-T cell therapy;
- •Use other intervention study drugs within 4 weeks before the first use of the drug;
- •Any anti-tumor treatment received within 4 weeks before the first use of the drug;
- •Plan to vaccinate live attenuated vaccine within 4 weeks before the first use of the drug or during the study period;
- •Have received systemic glucocorticoid or other immunosuppressive therapy within 14 days before the first use of the drug;
- •With known central nervous system (CNS) leukemia infiltration;
- •ECG examination during screening period showed that QTcF>450 ms for males and 470 ms for females;
- •Major organ surgery within 4 weeks before the first use of the drug;
- •Received radiotherapy within 4 weeks before the first use of the drug;
- •There is an active infectious disease with clinical significance, which needs intravenous antibiotic treatment, and the investigator and sponsor judge that the patient is not suitable to participate in the clinical trial;
- •Chronic or acute active hepatitis B virus or hepatitis C virus infection;
- •Known active tuberculosis or active syphilis;
- •Known history of human immunodeficiency virus (HIV) infection；
- •Have received immunotherapy and have ≥ grade 3 immune related adverse events (irAE);
- •History of serious cardiovascular and cerebrovascular diseases;
- •History of other malignant tumors within 5 years before enrollment;
- •Breastfeeding patients；
- •Patients with known prior hypersensitivity to human or humanized monoclonal antibodies, or hypersensitivity to any of the components of QLF32101；
- •Have uncontrollable concomitant diseases or other diseases judged by the investigator to be unsuitable for participation in this study.
研究组 & 干预措施
QLF32101
single arm with QLF32101 treatment
干预措施: QLF32101 (Drug)
结局指标
主要结局
Dose-limiting toxicity(DLT)
时间窗: 28 Days
Maximum tolerated dose(MTD)
时间窗: 28 Days
Recommended Phase II Dose (RP2D)
时间窗: through study completion, an average of 1 year
R/R AML: cCR rate; Medium and high risk MDS: ORR (CR+complete remission of bone marrow [mCR]+PR+hematological improvement [HI]).
时间窗: through study completion, an average of 1 year
次要结局
- Safety index:TEAEs,TRAEs,SAERs,TRSAEs.(through study completion, an average of 1 year)
- PK parameter(through study completion, an average of 1 year)
- Serum titer of ADAs against QLF32101(through study completion, an average of 1 year)