NCT02920697已完成1 期
Phase I Dose-escalation Study of Oral Administration of the Selective Bcl2 Inhibitor S 55746 in Patients With Refractory or Relapsed Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma
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
- 65
- 试验地点
- 18
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The purpose of this study is to determine the safety profile and tolerability of S 55746 in patients with CLL, B-Cell NHL and MM, in terms of Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D) through safety profile (DLT, MTD), PK profile, PD profile and preliminary efficacy.
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
- •Women or men aged >/=18 years
- •Patients with a measurable histologically confirmed Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Diffuse Large B-Cell Lymphoma (DLBCL), Small Lymphocytic Lymphoma (SLL) and Marginal Zone Lymphoma (MZL) (Arm A), or patients with an evaluable immunophenotypically confirmed CLL (Arm B), or patients with a measurable Multiple Myeloma t(11;14) (arm A expansion part) according to International Myeloma Working Group (IMWG) criteria
- •Relapsed after or refractory disease to standard treatments, and require treatment in the opinion of the investigator
- •Estimated life expectancy > 12 weeks
- •World Health Organization (WHO) performance status 0-2
- •Adequate bone marrow, renal and hepatic functions
- •No evidence or treatment for another malignancy within 2 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed
- •Additional inclusion criteria for food interaction cohort:
- •B-cell NHL patients at low risk of tumour lysis syndrome (TLS)
- •Recent/concomitant treatment altering gastric pH
排除标准
- •Previous treatment with a BH3 mimetic
- •Previous therapy for the studied disease within 3 weeks before first intake
- •Radioimmunotherapy, radiotherapy within 8 weeks before first intake
- •Major surgery within 3 weeks before first day of study drug dosing
- •Corticosteroids >= 20 mg prednisone equivalent per day within 7 days before first intake
- •Anticoagulant oral drugs, aspirin > 325 mg/day within 7 days prior to first S 55746 intake
- •Positive direct antiglobulin test (Coombs test) and haptoglobin below normal value
- •Prior allogenic stem cell transplant
- •Autologous stem cell transplant within 3 months before first intake
- •NHL patients diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukaemia
- •Human immunodeficiency virus (HIV)
- •Known acute or chronic hepatitis B or hepatitis C
- •Impaired cardiac function
- •Medications known to prolong corrected QT (QTc) interval
- •History or/ clinically suspicious for cancer- related Central Nervous System disease
- •Solitary extramedullary plasmacytoma
- •Laboratory Signs of TLS
- •Strong or moderate CYP3A4 inhibitors/inducers (treatment, food or drink products)
- •Treatment highly metabolized by the CYP3A4 or CYP2D6 and/or substrates with a narrow therapeutic index, multienzyme and/or OATP and/or P-gp substrates or herbal products.
- •Known hypersensitivity to rasburicase
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency and other cellular metabolic disorders known to cause haemolytic anaemia
- •Patients receiving proton pump inhibitor
研究组 & 干预措施
B-cell Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)
Experimental
干预措施: S 55746 (Drug)
Chronic Lymphocytic Leukaemia (CLL)
Experimental
干预措施: S 55746 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: During cycle 1 (21 days)
The MTD is the highest drug dosage that is unlikely (\<25% posterior probability) to cause DLT in more than 33% of the treated patients in the first cycle of S 55746 treatment
Incidence of Adverse Events (AEs)
时间窗: From first dose until 30 days after the last dose intake
Characterized by severity and seriousness of AEs, laboratory abnormalities and other safety parameters such as electrocardiogram (ECG) changes
次要结局
- Apoptotic activity from blood samples(At Cycle 1(21 days))
- Objective Response Rate (ORR)(Up to study completion (maximum of 3 years))
- The pharmacokinetic (PK) profile of S 55746: Area Under the Curve [AUC](Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D4, C1D5, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8)
- Progression Free Survival (PFS)(From date of inclusion until the date of progression or date of death, whichever occurs first, assessed up to study completion (maximum of 3 years))
- Plasma concentration of S 55746(Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D4, C1D5, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8)
- The PK profile of S 55746: Maximal Concentration [Cmax](Pre-dose on Cycle 1 Day 1 (C1D1), C1D2, C1D3, C1D4, C1D5, C1D8, C1D9, C2D1 ; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10-12 hours post-dose on C1D1, C1D8)
- Duration of response(Up to study completion (maximum of 3 years))
- Clinical Benefit Rate (CBR)(Up to study completion (maximum of 3 years))
研究者
研究点 (18)
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