A Study to Evaluate MTM-H-001 Injection in Adult Participants With Relapsed or Refractory B-cell Malignancies

Официальное название

An Open-label, Single-arm, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Preliminary Efficacy of MTM-H-001 in the Treatment of Adult Participants With Relapsed or Refractory B-cell Malignancies (Archonc-001)

Обзор

This is an investigator-initiated, open-label, single-arm, dose-escalation and dose-expansion study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of MTM-H-001 in adult participants with relapsed/refractory (R/R) B-cell malignancies.

Вмешательства

• Препарат MTM-H-001 Injection
  Each participant receives MTM-H-001 Injection

Первичные конечные точки

• Incidence of Dose-Limiting Toxicity (DLT) [Срок оценки: 42 days following first dose of MTM-H-001 for each participant]

Вторичные конечные точки (7)

• Objective response rate (ORR) [Срок оценки: Throughout the study, up to 24 months]
• Disease control rate (DCR) [Срок оценки: Throughout the study, up to 24 months]
• Time to response (TTR) [Срок оценки: Throughout the study, up to 24 months]
• Duration of response (DOR) [Срок оценки: Throughout the study, up to 24 months]
• Event-free survival (EFS) [Срок оценки: Throughout the study, up to 24 months]
• Progression free survival (PFS) [Срок оценки: Throughout the study, up to 24 months]
• Overall survival (OS) [Срок оценки: Throughout the study, up to 24 months]

Критерии участия

Критерии включения

• Male or female, aged 18 - 75 years old (inclusive);
• The participant or his/her legally acceptable representative gives consent to this clinical study participation and signs an Informed Consent Form (ICF) indicating their understanding of the objectives and procedures of the clinical study and willingness to participate in the study;
• Participants with histopathologically and immunohistochemically confirmed Non-Hodgkin B-cell Lymphoma (B-NHL) according to the 2016 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (CLL/SLL diagnosed in accordance with 2018 iwCLL criteria)
• Relapsed or refractory disease after receiving at least two prior lines of standard therapy, or relapsed or refractory disease after receiving autologous hematopoietic stem cell transplant (ASCT) (if applicable).
• Adequate major organ function, defined as meeting the following criteria:

• Hematology: Hemoglobin (Hb) ≥80 g/L; absolute neutrophil count (ANC) ≥1.0×10\^9/L; and platelet count (PLT) ≥75×10\^9/L;
• Coagulation: International Normalized Ratio (INR) ≤1.5×Upper Limit of Normal (ULN) and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN;
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0×Upper Limit of Normal (ULN);
• Serum Total Bilirubin (TBIL) ≤1.5×ULN (except for participants with documented Gilbert's syndrome);
• Blood creatinine (Cre) ≤1.5×ULN, or calculated creatinine clearance (Ccr) ≥50 mL/min (using the Cockcroft-Gault formula);
• Cardiac function: Good hemodynamic stability, Left Ventricular Ejection Fraction (LVEF) ≥50%;
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2;
• Expected survival >3 months;
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and agree to use at least one effective contraceptive method throughout the study and within 6 months after the last treatment cycle.

Критерии исключения

• B-NHL participants with a history of Richter's transformation of chronic lymphocytic leukemia (CLL).
• Primary central nervous system (CNS) lymphoma, or malignant tumors involving the CNS.
• Burkitt's lymphoma/leukemia, primary mediastinal large B-cell lymphoma (LBCL).
• Known history of other malignancies within the past 5 years, excluding cured localized tumors (including cervical carcinoma in situ, basal cell carcinoma of the skin, and prostate carcinoma in situ, etc.);
• Active hepatitis B virus (HBV) infection;
• Active hepatitis C virus (HCV) infection;
• Active human immunodeficiency virus (HIV) infection or a past history of HIV infection;
• Uncontrolled active infection requiring intravenous treatment within one week prior to the first dose;
• Corrected QT interval using Fridericia (QTcF) is ≥450 ms (male) or ≥470 ms (female) according to the electrocardiography (ECG) examination results at screening;
• Currently experiencing or having experienced within the past 6 months any of the following:

• Congestive heart failure (New York Heart Association \[NYHA\] Class III-IV);
• Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg with medication treatment;
• Myocardial infarction, clinically significant arrhythmias, unstable angina, Torsades de Pointes, left bundle branch block or bifascicular block, coronary/peripheral artery bypass grafting, congenital long QT syndrome;
• Cerebrovascular accident, transient ischaemic attack;
• Symptomatic pulmonary embolism;
• History of any mental disorders (e.g., schizophrenia, bipolar disorder, eating disorders, major depression, or anxiety) as reported by the participant or documented in medical records;
• Pregnant or breastfeeding women.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences — Langfang

Идентификаторы

NCT: NCT07476378 · MTM-H-001-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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