A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Dose recommend for dose expansion (DRDE)
研究概览
简要总结
This is a multicenter, open-label Phase I dose escalation study to evaluate the safety and preliminary efficacy of the TT-01488 tablet, a non-covalent reversible BTK inhibitor, for the treatment of adult patients with B-cell malignancies.
详细描述
The study will consist of two parts, dose escalation and dose expansion. A modified 3+3 design will be used to guide the dose escalation and the determination of the dose recommended for dose expansion (DRDE). A sentinel cohort comprising of one subject will be enrolled at a starting dose of 50 mg q.d. Subsequently, patients will be enrolled according to the standard 3+3 dose escalation design to determine the DRDE. Once the DRDE has been selected, TT-01488 of DRDE will be further tested in the dose expansion cohort to verify the safety and preliminary efficacy as observed in the dose escalation cohorts. A recommended Phase II dose (RP2D) may be determined based on the totality of safety, pharmacokinetics, and efficacy data from the dose escalation cohorts and dose expansion cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Participants with histologically confirmed B-cell malignancy, failed or intolerant to either ≥ 2 prior standard/common regimens given in combination or sequentially OR have received 1 prior BTK-containing regimen, relapse/refractory, and with treatment indication:
- •CLL/SLL treated with prior immunochemistry or BTK inhibitor containing regimen;
- •DLBCL treated with prior CD20 or anthracyclines containing regimen;
- •Other types of B-cell NHL treated with prior CD20 containing regimen
- •Adequate organ function, defined by the following laboratory parameters:
- •Hematologic:
- •Absolute neutrophil count (ANC) ≥ 0.75×10^9/L, and ≥ 0.5×10^9/L if bone marrow involved
- •Platelets ≥ 50×10^9/L without transfusion within 7 days, and ≥ 30×10^9/L if bone marrow involved
- •Hemoglobin ≥ 8.0 g/dL without transfusion within 7 days, and ≥ 7.0 g/dL if bone marrow involved
- •Coagulation:
- •Prothrombin time (PT) ≤ 1.5 × ULN
- •Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
- •Renal function:
- •Creatinine clearance ≥ 30 mL/min estimated glomerular filtration rate based on Cockcroft-Gault formula
- •Liver function:
- •Total bilirubin ≤ 1.5 × ULN (unless due to Gilbert's disease)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN unless disease-related
排除标准
- •Women who are pregnant or lactating
- •Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years or which will not limit survival to < 2 years (Note: these cases must be discussed with the Medical Monitor and/or Investigator)
- •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or significant screening ECG abnormalities
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- •History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 60 days or with any of the following:
- •Active graft versus host disease (GvHD);
- •Cytopenias from incomplete blood cell count recovery post-transplant;
- •Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
- •Ongoing immunosuppressive therapy
- •Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation
研究组 & 干预措施
Dose Escalation for TT-01488
TT-01488 tablets will be administered once daily in a 28-day cycle in increasing strength in order to determine the recommended dose for dose expansion.
干预措施: TT-01488 Tablets (Drug)
Dose Expansion for TT-01488
TT-01488 tablets will be administered once daily in 28-day cycles to verify the safety and preliminary efficacy as observed in the dose escalation cohorts.
干预措施: TT-01488 Tablets (Drug)
结局指标
主要结局
Dose recommend for dose expansion (DRDE)
时间窗: 3 years
Safety and tolerability of TT-01488 as a single agent
Dose-Limiting Toxicity (DLT) of TT-01488
时间窗: Up to 28 days after first dose
Safety and tolerability of TT-01488 as a single agent
Maximum Tolerated Dose (MTD), if reached, of TT-01488
时间窗: Up to 28 days after first dose
Safety and tolerability of TT-01488 as a single agent
次要结局
- Area under the concentration time curve (AUC 0-t)(3 years)
- Apparent volume of distribution associated with the terminal phase (Vz/F)(3 years)
- Apparent clearance (CL/F)(3 years)
- Half-life (T1/2)(3 years)
- Mean Residence Time (MRT)(3 years)
- Objective Response Rate (ORR)(3 years)
- Duration of Response (DOR)(3 years)
- Progression free survival (PFS)(3 years)
- Overall survival (OS)(3 years)
- Maximum plasma concentration (Cmax)(3 years)
- Time to Maximum Plasma Concentration (Tmax)(3 years)
- Disease Control Rate (DCR)(3 years)
- Number of participants with treatment-related adverse events (AEs)(3 years)