A Multicentre, Open-label, Single-arm, Phase I/II Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of Liposomal Mitoxantrone Hydrochloride Injection Combined With Pegaspargase in the Treatment of NKTCL
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)
研究概览
简要总结
This is a multicentre, open-label, single-arm, phase I/II clinical study to evaluate the safety, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with pegaspargase in patients with extranodal natural killer/T-cell lymphoma, nasal type (NKTCL).
详细描述
This is a multicentre, open-label, single-arm, phase I/II clinical study with a dose-escalation stage (part 1) and a dose-expansion stage (part 2). In part 1, patients with treatment-naïve, relapsed/refractory extranodal natural killer/T-cell lymphoma (nasal type) will be assigned to receive sequentially higher doses of liposomal mitoxantrone hydrochloride plus a standard dose of pegaspargase every 21 days (a cycle). The dose escalation initially will follow an accelerated titration design for the first two dosing groups, then follow a classic 3+3 design. All dose-escalation decisions will be based on the safety data generated from the currently highest dose group. The maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of liposomal mitoxantrone hydrochloride will be determined in part 1. In part 2, additional patients will be recruited into two groups,the treatment-naïve group and the relapsed or refractory group, to receive liposomal mitoxantrone hydrochloride at the RP2D combined with a standard dose of pegaspargase. All patients will receive the treatment until disease progression, or observation of unacceptable grade 3 drug-related adverse events (a maximum of 6 cycles).
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects fully understand and voluntarily participate in this study and sign informed consent;
- •Age ≥18, ≤75 years, no gender limitation;
- •Histologically confirmed diagnosis of treatment-naïve, relapsed or refractory extranodal NK/T-cell lymphoma nasal type (NKTCL);
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- •At least one measurable lesion as per Lugano 2014 criteria;
- •Adequate bone marrow, liver, renal and coagulation function
排除标准
- •Known central nervous system involvement caused by lymphoma;
- •Known infiltration of the bone marrow according to criteria for leukemia (≥20% myeloblast in the blood or bone marrow);
- •Known hemophagocytic syndrome;
- •History of allergy and contraindications to mitoxantrone hydrochloride and/or asparaginase/ pegaspargase;
- •Chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks of the first dose of the study drug (2 weeks for the local radiation therapy for pain relief);
- •Life expectancy < 3 months
- •Impaired cardiac function or serious cardiac disease;
- •Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other active viral infection;
- •Acute symptomatic or chronic pancreatitis within 4 weeks prior to screening;
- •History of, or known additional tumor (exception: non-melanoma skin cancer (in situ) and cervical cancer (in situ) which have been cured and have not recurred within 5 years);
- •History of solid organ transplantation, autologous hematopoietic stem cell transplantation within 6 months prior to screening, or allogeneic hematopoietic stem cell transplantation before screening;
- •Major surgery within 4 weeks prior to screening. Or have a surgical schedule during the study period;
- •A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator;
- •Uncontrolled diabetes at screening;
- •Known alcohol or drug abuse;
- •Known psychiatric disorders or cognitive disorder;
- •17. Pregnant or breastfeeding women, or patients who are expecting to conceive or father in 12 months (starting with the screening visit)；
- •Not suitable for this study as determined by the investigator due to other reasons.
结局指标
主要结局
Part 2 (relapsed or refractory patients):The percentage of patients who achieve complete response (CR)
时间窗: up to 26 weeks
CR rates at the end of treatment(including chemotherapy and radiation)
Part 1：dose limiting toxicities (DLTs)
时间窗: Cycle 1 (a cycle = 21 days)
The incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams
Part 2 (relapsed or refractory patients):The percentage of patients who achieve partial response (PR)
时间窗: up to 26 weeks
PR rates at the end of treatment(including chemotherapy and radiation)
Part 2 (treatment-naïve patients):The percentage of patients who achieve complete response (CR)
时间窗: up to 18 weeks
CR rates at the end of chemotherapy
次要结局
- Part 1 the preliminary antitumor efficacy：overall response rate (ORR)(up to 26 weeks)
- Part 1 the preliminary antitumor efficacy:disease control rate (DCR)(up to 26 weeks)
- Part 1: The pharmacokinetic parameters AUC0-t(At the end of Cycle 1 and Cycle 3 (each cycle is 21 days))
- Part 2 (relapsed or refractory patients): The preliminary antitumor efficacy(up to 26 weeks)
- Part 1: The pharmacokinetic parameters Cmax(At the end of Cycle 1 and Cycle 3 (each cycle is 21 days))
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy overall response rate (ORR)(up to 26 weeks)
- Part 2 (treatment-naïve patients):The preliminary safety index(through study completion, an average of 1 year)
- Part 1 the preliminary antitumor efficacy: complete response rate (CR)(up to 26 weeks)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy complete response rate (CR)(up to 26 weeks)
- Part 2 (treatment-naïve patients):The preliminary antitumor efficacy disease control rate (DCR)(up to 26 weeks)