Phase I Clinical Study of TQB2618 Injection in Combination With Demethylation Drugs in Patients With Recurrent/Refractory Acute Myeloid Leukemia, Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Recommended Phase II Dose (RP2D)
研究概览
简要总结
This project is an open, dose escalation and expansion phase I clinical study. The first phase is a dose escalation study, and the second phase is a dose expansion study based on the Maximum tolerated dose (MTD) / Recommended Phase II Dose (RP2D) obtained in the first phase. The purpose is to evaluate the tolerability and initially evaluate the antitumor efficacy of TQB2618 injection combined with demethylation drugs in patients with recurrent/refractory acute myeloid leukemia, myelodysplastic syndromes.
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
- •1 Subjects with medium-high risk recurrent/refractory International Prognostic Scoring System (IPSS-R) myelodysplastic syndromes(MDS) and acute myelocytic leukemia(AML) clearly diagnosed by pathology, who were intolerant to other medications and judged by the investigator to have no other appropriate treatment.
- •2 ≥18 years old; Eastern Cooperative Oncology Group (ECOG) physical status: 0-2; at least 3 months expected survival period.
- •3 The function of main organs is normal.
- •4 Subjects must need to adopt effective methods of contraception.
- •5 Subjects voluntarily joined the study, signed informed consent form, and with good compliance.
排除标准
- •1 Patients has had or is currently having other malignant tumors within 3 years. The following two conditions can be included in the group: other malignant tumors treated with a single operation to achieved 5 consecutive years of disease free survival (DFS)s. Cured cervical carcinoma in situ, non-melanoma skin cancer, nasopharyngeal carcinoma and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)].
- •2 Patients diagnosed with acute promyelocytic leukemia or Philadelphia Chromosome-Positive Acute Myeloid Leukemia (Ph+AML) , or low-risk relapsed and refractory AML who only received second-line therapy;
- •3 The non-hematologic toxicity of previous antitumor treatment is not recovered to ≤ grade 1 (excluding hair loss).
- •4 Received major surgical treatment, open biopsy or obvious traumatic injury within 4 weeks before treatment.
- •5 The subjects had any history of bleeding or coagulopathy or who were being treated with anticoagulant.
- •6 Subjects had an arteriovenous thrombosis event within 6 months.
- •7 History of drug abuse, alcohol or drug abuse or mental disorder. Subjects who have epilepsy and require treatment.
- •8 Poor blood pressure control (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100 mmHg);
- •9 Subjects who had received allogeneic stem cell transplantation or autologous stem cell transplantation within 3 months；
- •10 Subjects with ≥ grade 2 myocardial ischemia or infarction, arrhythmia, prolonged QTc interval (including male QTc ≥450ms, female QTc ≥470ms) and ≥ grade 2 congestive heart failure with New York Heart Association (NYHA )classification；
- •11 Active or uncontrolled severe infection ≥common terminology criteria for adverse events （CTCAE） grade 2 infection)；
- •12 Subjects with active hepatitis.
- •13 The subjects was diagnosed with renal failure and required hemodialysis or peritoneal dialysis.
- •14 History of immunodeficiency, including positive human immunodeficiency virus (HIV) test or other acquired, congenital immunodeficiency disease, or history of organ transplantation.
- •15 Poor control of diabetes (fasting glucose GLU > 10mmol/L);
- •16 Subjects who have received radiation therapy or the treatment of proprietary Chinese medicines with anti-tumor indications clearly stated in the National Medical Products Administration (NMPA) approved drug instructions within 4 weeks of starting treatment.
- •17 Uncontrolled pleural effusion, pericardial effusion or ascites;
- •18 Subjects with central nervous system aggression;
- •19 Vaccination history of live attenuated vaccine before 4 weeks of starting treatment, or planned vaccination of live attenuated vaccine during the study period.
- •20 History of severe allergy to study drugs and pharmaceutical excipients .
- •21 Subjects diagnosed with active autoimmune disease within 2 years before starting treatment.
- •22 Receiving any other investigational agent within 4 weeks before first dose.
- •23 According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subject or affect the completion of the study.
研究组 & 干预措施
TQB2618 injection
TQB2618 injection combined with demethylation drugs, 28 days as a treatment cycle until the disease progresses or the investigator judges that it is not suitable for subject to continue to take medicine.
干预措施: TQB2618 injection azacitidine, AZA decitabine, DAC (Drug)
结局指标
主要结局
Recommended Phase II Dose (RP2D)
时间窗: Baseline up to 78 weeks
To evaluate RP2D of TQB2618 injection combined with demethylation drugs in patients with recurrent/refractory acute myeloid leukemia, myelodysplastic syndromes.
Maximum tolerated dose (MTD)
时间窗: Baseline up to 78 weeks
To evaluate MTD of TQB2618 injection combined with demethylation drugs in patients with recurrent/refractory acute myeloid leukemia, myelodysplastic syndromes.
Dose limited toxicity (DLT)
时间窗: Baseline up to 78 weeks
To evaluate DLT of TQB2618 injection combined with demethylation drugs in patients with recurrent/refractory acute myeloid leukemia, myelodysplastic syndromes.
Objective Response Rate
时间窗: Baseline up to 78 weeks
To evaluate ORR of TQB2618 injection combined with demethylation drugs in patients with recurrent/refractory acute myeloid leukemia, myelodysplastic syndromes.
次要结局
- Adverse events (AE)(Baseline up to 92 weeks)
- Receptor occupation (RO)(Baseline up to 92 weeks)
- anti-drug antibody (ADA)/ neutralizing antibody (Nab)(Baseline up to 92 weeks)
- Progress Free Survival (PFS) Progress Free Survival (PFS)(up to 92weeks)
- Duration of Response (DOR)(up to 92weeks)
- Disease control rate (DCR)(up to 92weeks)