Phase I Dose Escalation Study of KW-0761 in Patients With Relapsed Adult T-Cell Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a Phase I label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell lymphoma (PTCL).
详细描述
This is a Phase I open-label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL). This study is designed to evaluate safety, pharmacokinetics, immunogenicity and preliminary efficacy. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose (RPIID) have been established.
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
- 20 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of a CCR4-positive ATL and PTCL that is any of the following:
- •A. ATL (Adult T-Cell Leukemia-Lymphoma)
- •Seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody;
- •Acute, Lymphoma, or Chronic phase with high-risk factors (within 14 days before the study entry);
- •B. PTCL (Peripheral T-Cell Lymphoma)
- •Includes Mycosis Fungoides and Sezary Syndrome;
- •2: Relapsed to the latest standard chemotherapy;
- •3: Received at least one prior chemotherapy;
- •4: After 4 weeks from a prior therapy;
- •5: Have measurable disease;
- •6:Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1;
- •7: Male or female, at least 20 years and not older than 70 years of age;
- •8: Signed written informed consent;
- •9: Stay in hospital for 4 weeks;
- •10: HBs antigen: negative, HBV-DNA: below the limit of quantification (within 14 days before the study entry);
- •11: Adequate bone marrow, hepatic and cardiac function including the followings:
- •Neutrophil count ≥ 1,500 /mm3,
- •Platelets ≥ 75,000 /mm3,
- •Hemoglobin ≥ 8.0 g/dL
- •Serum creatinine ≤ 1.5 x ULN;
- •Serum SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN (≤ 5.0 x ULN if considered due to disease involvement in liver);
- •Serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if considered due to disease involvement in liver)
- •Serum calcium ≤ 11.0 mg/dL
- •PaO2 ≥ 65 mmHg or SaO2 ≥ 90%
- •No clinically significant Electrocardiogram abnormality
- •Left Ventricular Ejection Fraction ≥ 50% [by ECHO or MUGA]
排除标准
- •Co-existing active infection or any co-existing medical condition that may compromise the safety of patients during the study, affect the patient's ability to complete the study, or interfere with interpretation of study results;
- •Active tuberculosis;
- •Prior stem cell transplantation;
- •Myocardial infarction (within 12 months prior to the study entry);
- •Concurrent acute or chronic hepatitis, or cirrhosis;
- •Anti-HCV: positive, Anti-HIV: positive
- •Concurrent active malignant disease;
- •Known allergic reaction to antibody therapy;
- •Concomitant treatment with systemic steroids;
- •Prior and Concurrent psychiatric disorder including dementia, epilepsy or any other CNS diseases;
- •Evidence of CNS metastasis at baseline;
- •Prior and Concurrent spinal cord disease;
- •Radiation therapy for bulky mass disease at the time of study entry or considered to require radiation therapy during the study;
- •Female patients who are pregnant or breast feeding;
- •Female patients of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards;
- •Treatment with any other investigational agent within the 4 months prior to study entry;
- •For any reason is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator.
研究组 & 干预措施
1
KW-0761
干预措施: KW-0761 (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 28 days
Subjects who were properly monitored for DLTs were to be analyzed to determine the number of subjects with a DLT by dose level.
Maximum Tolerated Dose (MTD)
时间窗: 28 days
The dose level at which Dose-Limiting Toxicity (DLT) was recognized was to be regarded as Maximum Tolerated Dose (MTD), and the dose level below MTD by one level was to be regarded as the recommended dose level (when MTD was not reached, 1.0 mg/kg was to be regarded as the recommended dose level) and 3 more subjects were to be newly added to the recommended dose level.
Pharmacokinetics-Plasma KW-0761 Concentrations
时间窗: 0-7 days post final dose
Plasma KW-0761 concentrations were to be summarized in tabular form with the descriptive statistics on a dose-by-dose basis. Individual and mean (+ standard deviation) plasma KW-0761 concentrations on an actual or logarithmic scale were to be plotted against the time of blood sampling.
Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (AUC0-7 Days)
时间窗: 0-7 days post final dose
The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (t1/2)
时间窗: 0 to 28 days post final dose and follow-up examinations (1 month and 2 months after the end of the post-dosing observation period).
The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
次要结局
- Antitumor Effect(50 days)
- Time to Progression (TTP)(Baseline to response)