Phase I/II, International, Multicentre, Open-label, Non-randomised, Non-comparative, Study Evaluating the Safety, Tolerability and Clinical Activity of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Azacitidine in Patients With Acute Myeloid Leukaemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 7
- 主要终点
- Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 with azacitidine in patients with acute myeloid leukaemia.
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
- •Patients aged ≥ 18 years
- •Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization 2016 classification (Arber, 2016) excluding acute promyelocytic leukaemia (APL, French American-British M3 classification) with: relapsed or refractory disease and without established alternative therapy, or secondary to MyeloDysplastic Syndrome and without established alternative therapy or, newly diagnosed AML, not previously treated for AML and who are not candidate for intensive chemotherapy due to age or comorbidities.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.
排除标准
- •Previous myeloproliferative syndrome (MPS).
- •Patients previously treated with any Mcl-1 inhibitor.
- •Patients who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 2 toxicity (except alopecia of any grade) according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 5.0, prior to the first IMP administration.
- •Severe or uncontrolled active acute or chronic infection.
- •Uncontrolled hepatitis B or C infection.
- •Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.
- •Troponin > ULN (Upper Limit of reference range) or Troponin T > ULN if Troponin I cannot be assessed.
- •Clinically significant cardiac dysfunction (including New York Heart Association class ≥II heart failure, Left Ventricular Ejection Fraction (LVEF) < 50% as assessed by echocardiography (ECHO) or Multi-Gated Acquisition (MUGA) scan).
- •QT prolongation defined as QTc (QT interval corrected for heart rate) interval (corrected with Fridericia's formula) > 450 ms for males and > 470 ms for females, obtained from triplicate 12-lead ECG.
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
- •Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 95 mmHg).
研究组 & 干预措施
S64315 (also referred as MIK665) with azacitidine
干预措施: S 64315 (also referred as MIK665) and azacitidine (Drug)
结局指标
主要结局
Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)
时间窗: an average of 6 months
Incidence and severity of AEs according to NCI CTCAE v5.0
Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)
时间窗: Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)
Incidence and severity of SAEs according to NCI CTCAE v5.0
Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)
时间窗: Day -13 to Cycle 1 Day 28 (each cycle is 28 days)
Incidence of DLTs starting from the Lead-In Dose period to the end of the first cycle of treatment of S64315 in combination with azacitidine.
Dose Intensity for Azacitidine (Phase I - Dose Escalation)
时间窗: Through study completion, an average of 6 months
Number of Participants With Dose Interruptions (Phase I - Dose Escalation)
时间窗: Through study completion, an average of 6 months
Number of Participants With Dose Reductions (Phase I - Dose Escalation)
时间窗: Through study completion, an average of 6 months
Dose Intensity for S64315 (Phase I - Dose Escalation)
时间窗: Through study completion, an average of 6 months
次要结局
- Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation)(At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days))
- Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)(Through study completion, an average of 6 months)
- Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)(Through study completion, an average of 6 months)
- Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation)(At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days))