Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Liposomal Mitoxantrone Hydrochloride Injection Combined With Cyclophosphamide, Vincristine and Prednisone in the Treatment of Untreated PTCL
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Dose-finding stage: The incidence of dose limited toxicities (DLTs)
研究概览
简要总结
This is a multicentre, open-label, single-arm, phase Ib clinical study to evaluate the safety, tolerability, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone in the frontline treatment of patients with peripheral T cell lymphoma (PTCL).
详细描述
The study is to investigate the safety, tolerability, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone in the frontline treatment of patients with PTCL by conducting in two stages, Dose-finding stage and Dose-expansion stage.In Dose-finding stage, patients with treatment-naïve PTCL will be assigned to receive sequentially higher doses of liposomal mitoxantrone hydrochloride ranging from 12 to 18 mg/m2 plus Cyclophosphamide, Vincristine and Prednisone (28 days per cycle). The dose escalation will follow the classic 3+3 design. The recommended Phase 2 dose (RP2D) of liposomal mitoxantrone hydrochloride will be determined according to the Dose-finding results. In Dose-expansion stage, additional patients will be recruited into two groups, the Q4W group（28 days per cycle）and the Q3W group（21 days per cycle）, to receive liposomal mitoxantrone hydrochloride at the RP2D combined with Cyclophosphamide, Vincristine and Prednisone. All patients will receive the treatment for the planned 6 cycles or until disease progression or unacceptable drug-related adverse events.
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 70 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, ≤70years, no gender limitation
- •Histologically confirmed diagnosis of treatment-naïve PTCL. Eligible histologies are limited to the following: Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS),Angioimmunoblastic T-cell lymphoma (AITL), ALK -positive Anaplastic Large cell Lymphoma（ALCL）, ALK-negative ALCL; Other PTCL that investigators consider to be appropriate to be enrolled
- •PTCL with fluorodeoxyglucose (FDG) avidity that can be evaluated by PET/CT
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
- •The following required baseline laboratory data: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count (PLT) ≥75×109/L, Hemoglobin(HB)≥ 80g/L, Total bilirubin (TBIL) ≤1.5X upper limit of normal (ULN) , Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN , Serum creatinine (Scr) ≤1.5X ULN
- •Females of childbearing potential must have a negative serum beta human chorionic gonadotrophin (β-hCG) pregnancy test result prior to enrollment and must agree to use an effective contraception method for the duration of the study treatment and 12 months after the last dose of study therapy
- •Males of reproductive potential must agree to use an effective contraceptive method for the duration of the study treatment and 12 months after the last dose of study therapy
排除标准
- •Current diagnosis of any of the following: extranodal natural killer/T-cell lymphoma, nasal type(NKTCL), Mycosis fungoides (MF)/ Sézary syndrome (SS), Primary cutaneous ALCL，and Adult T-cell leukemia/lymphoma
- •Leukemic phase of lymphoma (≥20% lymphoma cell in the bone marrow), or central nervous system (CNS) involvement, or hemophagocytic syndrome
- •Life expectancy < 6 months
- •History of allergy to anthracyclines or liposomes
- •History of contraindications to cyclophosphamide, vincristine or prednisone
- •Prior anti-lymphoma therapy except short-term or low-dose corticosteroid treatment
- •Impaired cardiac function or significant cardiac disease
- •Positive test results for HBsAg antigen and HBV-DNA, or hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody
- •Major surgery within 4～6weeks prior to screening. Or have a surgical schedule during the study
- •A serious infection within 4 weeks prior to screening and not suitable for the study according to the judgment of the investigator
- •Uncontrolled hypertension at screening
- •Uncontrolled diabetes at screening
- •History of active visceral hemorrhage in the recent 3 months prior to screening
- •History of other tumors in the past five years prior to screening. Patients with curable tumors (such as skin basal cell carcinoma, carcinoma in situ of the cervix or of the breast, intramucosal carcinoma in situ of the gastrointestinal tract or localized prostate cancer) could be enrolled after completely cured
- •History of solid organ transplantation
- •Known psychiatric disorders or cognitive disorder
- •Known alcohol or drug abuse
- •Pregnant or breastfeeding women
- •Not suitable for this study as determined by the investigator due to other reasons
结局指标
主要结局
Dose-finding stage: The incidence of dose limited toxicities (DLTs)
时间窗: Cycle 1 (28 days)
To identify the DLTs
Dose-finding stage:The incidence of AE and SAE
时间窗: up to 24 weeks
To identify the incidence of AE and SAE, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams
Dose-expansion stage: The incidence of AE and SAE
时间窗: up to 18-24 weeks
To identify the incidence of AE and SAE, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams
次要结局
- Dose-finding stage: progression-free survival（PFS）(Throughout study completion,an average of 18 months)
- Dose-finding stage: complete response(CR) rate(up to 24 weeks)
- Dose-finding stage: duration of complete response（DoCR）(Throughout study completion,an average of 18 months)
- Dose-finding stage: overall response rate (ORR)(up to 24 weeks)
- Dose-finding stage：the pharmacokinetic parameters Cmax(Cycle 1 to Cycle 6(each cycle is 28 days))
- Dose-finding stage：the pharmacokinetic parameters AUC0-t(Cycle 1 to Cycle 6(each cycle is 28 days))
- Dose-expansion stage: CR rate(up to 24 weeks)
- Dose-expansion stage: DoCR(Throughout study completion,an average of 18 months)
- Dose-expansion stage: ORR(up to 18-24 weeks)
- Dose-expansion stage: PFS(Throughout study completion,an average of 18 months)
- Dose-expansion stage: the pharmacokinetic parameters Cmax(Cycle 1(each cycle is 21or28 days))
- Dose-expansion stage: the pharmacokinetic parameters AUC0-t(Cycle 1(each cycle is 21or28 days))