Phase I, Open Label, Non-randomised, Non-comparative, Multi-center Study, Evaluating S65487, a Bcl-2 Inhibitor Intravenously Administered, in Patients With Relapsed or Refractory Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Multiple Myeloma or Chronic Lymphocytic Leukemia

Institut de Recherches Internationales Servier11 个研究点分布在 4 个国家目标入组 60 人开始时间: 2019年7月17日最近更新: 2024年10月16日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Institut de Recherches Internationales Servier
入组人数: 60
试验地点: 11
主要终点: Incidence of Dose Limiting Toxicity (DLT)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM) or Chronic Lymphocytic Leukemia (CLL).

详细描述

This study is designed in two parts: one part for dose escalation, one part for dose expansion.The dose escalation part will be followed by expansion part at the MTD(s)/RP2D(s)

This study will utilize an adaptative Bayesian Logistic Regression model to guide dose escalation and estimate the MTD(s) based on the Dose Limiting Toxicity (DLT) relationship(s) for S65487 in the indications.

研究设计

研究类型: Interventional
分配方式: Non 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

•Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia with relapsed or refractory disease without established alternative therapy. Or patients with measurable confirmed Multiple Myeloma (IMWG) with relapsed or refractory disease who have previously received at least three lines of treatment and without established alternative therapy. Or patients with histologically and measurable confirmed Non Hodgkin Lymphoma defined as Diffuse Large B cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), High-Grade B cell Lymphoma with relapsed or refractory disease who have received at least two lines of therapy (including rituximab) and without established alternative therapy. Or patients with Chronic Lymphocytic Leukemia (CLL) who have relapsed or are refractory (except treatment failure), as defined per iwCLL, from venetoclax treatment and without established alternative therapy.
•ECOG (Eastern Cooperative Oncology Group) performance status ≤
•For NHL, MM patients and CLL patients: haematological function (independent of any growth factor support) based on the last assessment performed before inclusion, defined as: absolute neutrophil count (ANC) ≥ 1 x 109/L, haemoglobin ≥ 8 g/dL, platelet count ≥ 50 x 109/L for NHL and MM patients, platelet count ≥ 30 x 109/L for CLL patients.
•For AML patients: circulating Blood White Cell count (WBC count) < 25 x 109/L (with or without use of hydroxycarbamide/leukapheresis) based on the last assessment performed before inclusion.
•Adequate renal function based on the last assessment performed before inclusion, assessed as Glomerular Filtration Rate (GFR) using Modification of Diet in Renal Disease (MDRD) Formula.
•Adequate hepatic function based on the last assessment performed before inclusion.

排除标准

•Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
•Participation in another interventional study at the same time or another interventional study requiring investigational treatment intake within 3 weeks or at least 5 half-lives (whichever is longer) prior to the first S65487 administration.
•Participant already enrolled in the study (informed consent signed) and has received at least one dose of S
•Patients who have not recovered from toxicity of previous anticancer therapy, including grade ≥ 2 non-hematologic toxicity, prior to the first IMP administration (including peripheral neurotoxicity). Certain toxicities will not be considered in this category (e.g. alopecia).
•Patients refractory to a previous treatment with a Bcl-2 inhibitor.
•For AML patients : Allogenic stem cell transplant within 3 months before the first IMP administration and/or patients who still receive immunosuppressive treatment within 3 months before the first IMP administration and/or patients with active Graft-versus-host disease within 3 months before the first IMP administration and/or patient who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration.
•For NHL, MM and CLL patients : Prior allogenic stem cell transplant before the first IMP administration and/or Autologous stem cell transplant within 3 months before the first IMP administration.

研究组 & 干预措施

S65487 - initial scheme

Experimental

干预措施: S65487- initial scheme (Drug)

S65487 - alternative scheme

Experimental

干预措施: S65487 - alternative scheme (Drug)

结局指标

主要结局

Incidence of Dose Limiting Toxicity (DLT)

时间窗: until the end of the first cycle (each cycle is 21days)

Safety criterion

Number of participants with dose reductions