A Study of BL-M11D1 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Официальное название

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

Обзор

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).

Вмешательства

• Препарат BL-M11D1
  Administration by intravenous infusion

Первичные конечные точки

• Phase Ia: Dose limiting toxicity (DLT) [Срок оценки: Up to 28 days after the first dose]
• Phase Ia: Maximum tolerated dose (MTD) [Срок оценки: Up to 28 days after the first dose]
• Phase Ib: Recommended Phase II Dose (RP2D) [Срок оценки: Up to 28 days after the first dose]

Вторичные конечные точки (11)

• Treatment-Emergent Adverse Event (TEAE) [Срок оценки: Up to approximately 24 months]
• Cmax [Срок оценки: Up to 28 days after the first dose]
• Tmax [Срок оценки: Up to 28 days after the first dose]
• T1/2 [Срок оценки: Up to 28 days after the first dose]
• AUC0-t [Срок оценки: Up to 28 days after the first dose]
• CL (Clearance) [Срок оценки: Up to 28 days after the first dose]
• Ctrough [Срок оценки: Up to 28 days after the first dose]
• ADA (anti-drug antibody) [Срок оценки: Up to approximately 24 months]
• Phase Ib: Objective Response Rate (ORR) [Срок оценки: Up to approximately 24 months]
• Phase Ib: Disease Control Rate (DCR) [Срок оценки: Up to approximately 24 months]
• Phase Ib: Duration of Response (DOR) [Срок оценки: Up to approximately 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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 \&gt; 150 mmHg or diastolic blood pressure \&gt; 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-M11D1.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 8 центров

• Anhui Provincial Hospital — Хэфэй
• Beijing Hospital — Пекин
• Institute of Hematology, the First Hospital of Harbin — Haerbin
• Shengjing Hospital of China Medical University — Шэньян
• Qilu Hospital of Shandong University — Цзинань
• Shanghai Tongji Hospital — Шанхай
• West China Hospital，Sichuan University — Чэнду
• Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences — Тяньцзинь

Идентификаторы

NCT: NCT05924750 · BL-M11D1-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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