A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BL-M11D1 in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 8
- 主要终点
- Phase Ia: Dose limiting toxicity (DLT)
研究概览
简要总结
Ia: To observe the safety and tolerability of BL-M11D1 in patients with relapsed/refractory acute myeloid leukemia to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of BL-M11D1. Ib: Further observe the safety and tolerability of BL-M11D1 at the recommended dose in phase Ia to determine the recommended dose in phase II clinical study (RP2D).
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;
- •Histologically and/or cytologically confirmed CD33-positive relapsed/refractory acute myeloid leukemia (AML);
- •Morphological assessment showing ≥5% blasts in the bone marrow;
- •ECOG performance status score ≤2;
- •Peripheral blood white blood cell count ≤25×10^9/L before the first dose;
- •Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
- •Organ function levels meet the requirements within 7 days before the first dose;
- •For premenopausal women with childbearing potential, a pregnancy test (serum/urine) must be performed within 7 days before starting treatment, and the result must be negative; they must not be breastfeeding. All enrolled patients (regardless of gender) must use adequate barrier contraception throughout the treatment period and for 6 months after treatment ends.
排除标准
- •Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia.
- •Antineoplastic therapy, including chemotherapy, biologic therapy, immunotherapy, definitive radiotherapy, major surgery (investigator-defined), or targeted therapy (including small-molecule tyrosine kinase inhibitors), has been administered within 4 weeks or 5 half-life cycles (whichever is shorter) before the first dose; Or palliative radiotherapy within 2 weeks before the first dose.
- •History of severe heart disease, such as left ventricular ejection fraction < 50%, history of symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of myocardial infarction, unstable angina, etc.
- •Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, and III degree atrioventricular block.
- •Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can only be controlled by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis).
- •Other malignancies diagnosed within 5 years before the first dose, except for radical basal cell carcinoma, squamous cell carcinoma, and/or radical resection carcinoma in situ.
- •Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg).
- •Patients with pulmonary disease grade ≥3 defined by CTCAE v5.0, current or previous interstitial lung disease (ILD).
- •Patients with central nervous system involvement.
- •Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M11D
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
- •Human immunodeficiency virus (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive; HBcAb positive and HBV-DNA copy number > lower detection limit) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower detection limit).
- •Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
- •Presence of pleural, abdominal, pelvic or pericardial effusion with clinical symptoms or requiring repeated drainage.
- •Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of last 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
Study treatment
Participants receive BL-M11D1 as intravenous infusion 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 Ia: Dose limiting toxicity (DLT)
时间窗: Up to 28 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 28 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 28 days after the first dose
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.
次要结局
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Cmax(Up to 28 days after the first dose)
- Tmax(Up to 28 days after the first dose)
- T1/2(Up to 28 days after the first dose)
- AUC0-t(Up to 28 days after the first dose)
- CL (Clearance)(Up to 28 days after the first dose)
- Ctrough(Up to 28 days after the first dose)
- 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)