NCT07288814尚未招募1 期
A Single-Arm, Open-Label Ib/II Study of Mitoxantrone Hydrochloride Liposome and Enlonstobart Combination Treatment in Patients With Relapsed or Refractory Peripheral T Cell Lymphoma（PTCL）
Sun Yet-Sen University Cancer Center0 个研究点目标入组 43 人开始时间: 2025年12月8日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 43
- 主要终点
- Phase Ib: Recommended Phase II Dose (RP2D)
研究概览
简要总结
To evaluate the safety of mitoxantrone hydrochloride liposome combined with enlonstobart in the treatment of relapsed or refractory peripheral T-cell lymphoma, to determine the optimal dosage of mitoxantrone hydrochloride liposome within the combination regimen, and to assess the efficacy of the combined therapy.
详细描述
This is a single-arm, phase Ib/II study to investigate the safety and efficacy of mitoxantrone hydrochloride liposome combined with enlonstobart in the treatment of relapsed and refractory peripheral T-cell lymphoma, and the optimal dose of mitoxantrone hydrochloride liposome. In the dose-escalation phase, the initial dose of mitoxantrone hydrochloride liposome injection was 16mg/m2, and two dose groups of 16mg/m2, 20 mg/m2, D1, q4w were designed. Enlonstobart was administered at a fixed dose of 360mg, D1, q4w. Dose-limiting toxicity (DLT) was assessed after cycle 1. Six cycles of induction therapy were planned. After induction therapy, if the response evaluation was CR/PR, maintenance treatment with enlonstobart (360mg, D1, q3w) could be performed.
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
- •Centrally confirmed histopathological/cytologic diagnosis of PTCL with the following subtypes:
- •Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS);
- •Systemic anaplastic large cell lymphoma (ALK+ and ALK-);
- •Follicular helper T (TFH) cell lymphoma of lymph nodes, including angioimmunoblastic, follicular, NOS;
- •and any other PTCL subtypes deemed by the investigator to be eligible for inclusion.
- •Voluntary participation in clinical study; Fully understand and informed the study and sign the written informed consent;
- •Age ≥18 years old, and ≤ 75 years old, regardless of gender;
- •Met the criteria of relapsed/refractory lymphoma: Relapsed lymphoma was defined as relapsed lymphoma more than 6 months after achieving complete remission (CR) after initial chemotherapy. Refractory lymphoma was defined as any of the following criteria: 1) tumor shrinkage < 50% or disease progression after at least 4 courses of standard chemotherapy; 2) achieved CR with standard chemotherapy, but relapsed within half a year;
- •ECOG performance status score: 0-2;
- •Expected survival time ≥3 months;
- •There must be at least one measurable or evaluable lesion that meets the Lugano 2014 criteria for lymphoma:
- •Measurable lesion: Nodal lesions with major diameter greater than 1.5cm and minor diameter greater than 1.0cm as assessed by PET/CT or Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI); Or the length of extranodal lesions >1.0cm; 2)Evaluable lesions: PET-CT showed increased uptake in lymph nodes or extranodal regions (higher than liver) and imaging features consistent with lymphoma; 8.Have adequate organ and bone marrow function, defined as follows:
- •Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L(≥1.0×109/L in patients with bone marrow involvement); platelet count (PLT) ≥ 75×109/L(≥50×109/L in patients with bone marrow involvement), hemoglobin (HGB) ≥ 8.0 g/dL; The patients had not received granulocyte growth factor, platelet transfusion, or red blood cell transfusion within 14 days before the examination;
- •Liver function: serum total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN, liver invasion ≤3.0×ULN); alanine aminotransferase (ALT) and aspartate transferase (AST) ≤2.5×ULN (liver invasion ≤5.0×ULN);
- •Renal function: serum creatinine (Cr) ≤1.5×ULN.
- •Coagulation function: International Normalized Ratio (INR) ≤1.5 × ULN; Prothrombin Time (PT), Activated PartialThromboplastin Time (APTT) ≤1.5×ULN (unless the subject is receiving anticoagulant therapy, And PT and APTT at screening were within the expected range for anticoagulant therapy).
- •Thyroid stimulating hormone (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) within the normal range ±10% (Note: non-autoimmune causes of abnormal TSH, FT3 and FT4 can be maintained in the normal range after replacement treatment of hypothyroidism can be enrolled).
- •9.Patients who had received previous antineoplastic therapy could not be enrolled until the toxicity of previous treatment returned to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade score ≤1 or the baseline level; 10.Women of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose of medication; Effective contraception should be used from the time of informed consent until 6 months after the last dose of study drug.
排除标准
- •Patients with hemophagocytic lymphohistiocytosis;
- •Patients with active infection or with obvious B symptoms and high fever should be excluded according to the comprehensive judgment of the investigators;
- •The subject's previous history of antineoplastic therapy meets one of the following conditions:
- •Failure to achieve CR or PR after previous treatment with mitoxantrone or mitoxantrone liposome, or relapse within 6 months after treatment;
- •Prior treatment with anthracyclines or anthraquinones and cumulative dose of doxorubicin > 550 mg/m2 (liposomal doxorubicin > 2000 mg/m2, epirubicin > 1000 mg/m2, pirarubicin > 1000 mg/m2, mitoxantrone > 160 mg/m2);
- •Received anti-tumor treatment (including chemotherapy, targeted therapy, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks or 5 half-lives (whichever came first) before the first use of the study drug;
- •patients who received autologous hematopoietic stem-cell transplantation or allogeneic hematopoietic stem-cell transplantation within 100 days of the first dose of treatment;
- •Hypersensitivity reaction to any study drug or its components;
- •Patients with known allergy to any component of the monoclonal antibody;
- •Patients with a known history of Human Immunodeficiency Virus (HIV) infection and/or acquired immunodeficiency syndrome;
- •Patients with active chronic hepatitis B or active hepatitis C. Hepatitis B SurfaceAntigen (HBsAg) or hepatitis B core Antibody (HBcAb) or Hepatitis C Virus (HCV) during the screening period HCV) antibody positive patients must be further tested for Hepatitis B Virus (HBV) DNA (no more than 1000 copies /mL or 500 IU/mL) and HCV RNA (no more than the lower limit of detection of the assay), Enrollment in the trial occurred after the exclusion of patients with active hepatitis B or hepatitis C infection requiring treatment. Hepatitis B virus (HBV) carriers, medically stable hepatitis B (DNA > 1000 copies /mL or 500IU/mL) and cured hepatitis C patients are eligible for enrollment.
- •Cardiac function and disease is one of the following:
- •long QTc syndrome or QTc interval >480 ms;
- •complete left bundle branch block, degree II or III atrioventricular block;
- •severe, uncontrolled arrhythmia requiring medical treatment;
- •New York College of Cardiology grade ≥ III;
- •cardiac ejection fraction (LVEF) less than 50%;
- •a history of myocardial infarction, unstable angina, major unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities within 6 months before recruitment;
- •Receive live attenuated vaccine (except influenza vaccine) within 4 weeks before enrollment or during the study period;
- •Previous or current concurrent cancer (except for effectively controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment within the previous five years);
- •Those with central nervous system involvement;
- •Lactating women;
- •Subjects receiving systemic glucocorticoid therapy or other immunosuppressive therapy for a condition within 14 days before starting study treatment (topical, ocular, intra-articular, nasal, and inhaled glucocorticoids were allowed (minimal systemic absorption); Short-term (≤ 7 days) use of glucocorticoids was permitted for preventive treatment (e.g., contrast allergy) or for the treatment of nonautoimmune conditions (e.g., delayed hypersensitivity from contact allergens).
- •Had undergone major surgery within 28 days before starting study treatment, or had undergone radiation therapy within the previous 90 days.
研究组 & 干预措施
Mitoxantrone hydrochloride liposome combined with enlonstobart
Experimental
干预措施: Mitoxantrone Hydrochloride Liposome & Enlonstobart (Drug)
结局指标
主要结局
Phase Ib: Recommended Phase II Dose (RP2D)
时间窗: through Phase Ib study completion, an average of 3 months
RP2D based on Phase Ib results
Phase Ib: Dose limited toxicities (DLTs)
时间窗: Cycle 1 (28 days)
Adverse events (AE) defined as DLT events per protocol
Phase II: Objective response rate (ORR)
时间窗: Up to 1 years
Response is assessed according to the 2014 lugano criteria
次要结局
- Complete response rate (CRR)(Up to 1 years)
- Progression-free survival（PFS）(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Disease control rate (DCR)(Up to 1 years)
- Adverse events(AE)(From the first day of medication to 28 days after the last dose)
研究者
Huiqiang Huang
Director, Head of Medical Oncology, Principal Investigator, Clinical Professor
Sun Yet-Sen University Cancer Center
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