A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M08D1 for Injection in Patients With Relapsed or Refractory Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Phase Ia: Dose limiting toxicity (DLT)
研究概览
简要总结
This study is an open-label, multicenter, dose-escalation and extended-enrollment, nonrandomized phase I study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M08D1 for injection in relapsed or refractory lymphoid malignancies.
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
- •Sign the informed consent form voluntarily and follow the protocol requirements;
- •Gender is not limited;
- •Age: ≥18 years old and ≤75 years old;
- •Expected survival time ≥3 months;
- •Recurrent or refractory lymphoid malignancies confirmed by histopathology and/or cytology that are incurable or for which no standard treatment is currently available;
- •Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years;
- •The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •Organ function level must meet the requirements;
- •Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
- •Urinary protein ≤2+ or ≤1000mg/24h;
- •For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and the patient must not be lactating; All enrolled patients (regardless of male or female) should use adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment;
- •Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.
排除标准
- •Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Palliative radiotherapy or traditional Chinese medicine with anti-tumor indications within 2 weeks before the first dose;
- •History of severe heart disease;
- •QT prolongation, complete left bundle branch block, III degree atrioventricular block;
- •Active autoimmune and inflammatory diseases;
- •Other malignant tumors diagnosed within 5 years before the first dose;
- •Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
- •Patients with poor glycemic control or with diabetic gangrene;
- •A history of ILD requiring steroid therapy or current ILD or grade ≥2 radiation pneumonitis;
- •Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
- •Patients with central nervous system involvement;
- •Had a history of or central nervous system disease;
- •Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any component of BL-M08D1 excipients;
- •Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
- •Active infection requiring systemic therapy within 4 weeks before the first dose of study drug;
- •Pleural, abdominal, pelvic or pericardial effusion requiring drainage and/or with symptoms within 4 weeks before the first dose of study drug;
- •Received another trial drug 4 weeks or 5 half-lives before the first dose;
- •Pregnant or lactating women;
- •Other conditions for participation in the trial were not considered appropriate by the investigator.
研究组 & 干预措施
BL-M08D1
Participants receive BL-M08D1 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: BL-M08D1 (Drug)
结局指标
主要结局
Phase Ia: Dose limiting toxicity (DLT)
时间窗: Up to 21 days after the first dose
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)
时间窗: Up to 21 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.
Phase Ib: Recommended Phase II Dose (RP2D)
时间窗: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-M08D1.
次要结局
- ADA (anti-drug antibody)(Up to approximately 24 months)
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)