NCT02979366已完成1 期
Phase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 9
- 主要终点
- Tolerability: Dose interruptions
研究概览
简要总结
The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Male or female aged ≥ 18 years;
- •Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):
- •with relapsed or refractory disease without established alternative therapy or
- •secondary to MDS treated at least by hypomethylating agent or
- •> 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative chemotherapy Or Patients with cytologically confirmed and documented MDS), in relapse or refractory after previous treatment line including at least one hypomethylating agent and have ≥10% bone marrow blasts;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Circulating white blood cells < 10^9 /L (with or without use of hydroxycarbamide).
- •Adequate renal function defined as:
- •Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m
- •LDH < 2 x ULN
- •Adequate hepatic function defined as:
- •AST and ALT ≤ 1.5 x ULN
- •Total bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome (confirmed by the UGT1A1 polymorphism analysis), who are excluded if total bilirubin>3.0 x ULN or direct bilirubin > 1.5 x ULN
- •Serum CK/CPK ≤2.5 x ULN.
排除标准
- •Unlikely to cooperate in the study.
- •Participant already enrolled in the study who has received at least one S64315 infusion.
- •Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
- •Participation in another interventional study requiring investigational treatment intake within 2 weeks or at least 5 half-lives (whichever is longer) prior to first dose of S64315 (participation in non-interventional registries or epidemiological studies is allowed).
- •Presence of ≥ CTCAE grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.03)
- •Unresolved ≥ CTCAE grade 2 diarrhoea or medical conditions associated with chronic diarrhoea (such as irritable bowel syndrome, inflammatory bowel disease)
- •Known carriers of HIV antibodies
- •Known history of significant liver disease
- •Uncontrolled hepatitis B or C infection
- •Known active or chronic pancreatitis
- •History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment.
研究组 & 干预措施
S64315 (also referred as MIK665) administered once a week
Experimental
干预措施: S64315 once a week (Drug)
S64315 (also referred as MIK665) administered twice a week
Experimental
干预措施: S64315 twice a week (Drug)
结局指标
主要结局
Tolerability: Dose interruptions
时间窗: From first dose until 30 days after the last dose administration
Tolerability: Dose reductions
时间窗: From first dose until 30 days after the last dose administration
Incidence of DLTs during the first cycle of treatment with single agent S64315
时间窗: 21-day cycle 1
Safety tolerance profile of S64315 assessed by:Incidence and severity of AEs
时间窗: From first dose until 30 days after the last dose administration
Tolerability: Dose intensity
时间窗: From first dose until 30 days after the last dose administration
次要结局
- Area under the concentration-time curve from zero (time of drug administration) to tlast (AUC last) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Time corresponding to Clast (tlast) in plasma.(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- total Clearance (CL)(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Renal clearance (CLR)(only D1 of cycle 1)
- Preliminary efficacy assessment according to Cheson criteria (adapted for each disease)(From first dose until 30 days after the last dose administration)
- Concentration at the end of infusion (C inf) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Last quantifiable observed concentration (Clast) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Cumulative amount of a compound excreted in the urine (Ae)(only D1 of cycle 1)
- Area Under the Curve (AUC) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Terminal elimination half-life (t½,z) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Volume of distribution at steady-state (Vss) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Time corresponding to end of infusion (tinf/tend) in plasma(D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.)
- Ae expressed as a percentage of the dose (fe) in urine(only D1 of cycle 1)
研究者
研究点 (9)
Loading locations...
相似试验
招募中
1 期
A study to test different doses of BI 765049 alone and in combination with ezabenlimab in Asian people with advanced cancer (solid tumours) positive for B7-H6B7-H6-positive GC, CRC, PDAC, HCC, HNSCC, or NSCLC patientsJPRN-jRCT2031230596Hagimori Kenta70
进行中（未招募）
1 期
A first in man study of RGT100 injection into solid tumorsEUCTR2016-003028-22-DERigontec GmbH15
进行中（未招募）
1 期
A first in man study of RGT100 injection into solid tumorsAdvanced or recurrent tumorsMedDRA version: 20.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000020962MedDRA version: 20.0 Level: LLT Classification code 10024700 Term: Liver metastases System Organ Class: 100000020848MedDRA version: 20.0 Level: LLT Classification code 10024717 Term: Liver tumor System Organ Class: 100000020895EUCTR2016-003028-22-FRRigontec GmbH15
进行中（未招募）
1 期
A first in man study of RGT100 injection into solid tumorsEUCTR2016-003028-22-GBRigontec GmbH15
进行中（未招募）
1 期
A first in man study of RGT100 injection into solid tumorsEUCTR2016-003028-22-ESRigontec GmbH15