A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of BL-M11D1 for Injection in Patients With Relapsed/Refractory Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Phase Ib: Recommended Phase II Dose (RP2D)
研究概览
简要总结
This study is an open-label, multicenter, non-randomized Phase Ib/II clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of BL-M11D1 for injection in patients with relapsed/refractory myelodysplastic syndromes.
详细描述
The study consists of two phases: a dose-exploration phase (Phase Ib) and a dose-expansion phase (Phase II).
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
- •Voluntarily sign the informed consent form and comply with the protocol requirements;
- •No gender restrictions;
- •Age: ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Relapsed/refractory CD33+ MDS;
- •Morphological assessment showing blasts in bone marrow ≥5% and <20%;
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
- •Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
- •Meet the required organ function levels;
- •For premenopausal women of childbearing potential, a pregnancy test (serum/urine) must be negative within 7 days before starting treatment, and they must not be breastfeeding; all enrolled trial participants (regardless of gender) must practice adequate barrier contraception throughout the entire treatment period and for 6 months after treatment completion.
排除标准
- •Use of chemotherapy, biotherapy, immunotherapy, etc., within 4 weeks or 5 half-lives prior to the first dose;
- •Presence of uncorrected folate deficiency or vitamin B12 deficiency, etc.;
- •History of severe cardiovascular or cerebrovascular disease;
- •Thromboembolic events requiring therapeutic intervention within 6 months prior to screening;
- •Active autoimmune diseases and inflammatory diseases;
- •History of extensive bowel resection or presence of Crohn's disease, ulcerative colitis, chronic diarrhea, or intestinal obstruction;
- •Diagnosis of another malignancy within 5 years prior to the first dose;
- •Poorly controlled hypertension;
- •Poorly controlled hyperglycemia or diabetes mellitus;
- •Pulmonary diseases classified as Grade ≥3 according to CTCAE v6.0, etc.;
- •Trial participants with central nervous system involvement;
- •Trial participants with extramedullary involvement;
- •Trial participants with a history of allergy to recombinant humanized antibodies or chimeric human-mouse antibodies, or hypersensitivity to any excipient component of BL-M11D1;
- •Prior organ transplantation or hematopoietic stem cell transplantation;
- •Positive for human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active fungal, bacterial, or viral infections;
- •History of severe neurological or psychiatric disorders;
- •Trial participants with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to signing informed consent;
- •Presence of clinically symptomatic pleural, peritoneal, or pericardial effusion requiring repeated drainage;
- •Participation in another clinical trial within 4 weeks or 5 half-lives prior to the first dose;
- •Pregnant or breastfeeding women;
- •Other conditions deemed by the investigator to make the participant unsuitable for participation in this clinical trial.
研究组 & 干预措施
BL-M11D1
Participants receive BL-M11D1 for the first cycle (4 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-M11D1 (Drug)
结局指标
主要结局
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-M11D1.
Phase Ib: Treatment-Emergent Adverse Event (TEAE)
时间窗: Up to approximately 24 months
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M11D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M11D1.
Phase II: Objective Response Rate (ORR)
时间窗: Up to approximately 24 months
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Phase II: Complete Response (CR)
时间窗: Up to approximately 24 months
Complete Response (CR) is defined as the disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) having a short axis diameter reduced to \<10 mm.
次要结局
- 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)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- Phase II: Duration of Response (DOR)(Up to approximately 24 months)
- Phase II: Hematologic Improvement (HI)(Up to approximately 24 months)
- Phase II: AML Transformation Rate(Up to approximately 24 months)