A Clinical Study to Evaluate the Safety and Preliminary Efficacy of QI-019A in Patients With Relapsed/Refractory Multiple Myeloma.

Обзор

This is a single-arm, open-label, single-center clinical trial to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of QI-019A in patients with relapsed/refractory multiple myeloma.

Подробное описание

This investigator-initiated clinical study aims to evaluate QI-019A, the lentiviral vector that carries a BCMA/CD19-targeted CAR, in patients with relapsed or refractory multiple myeloma (MM). The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy.

Вмешательства

• Препарат QI-019A Injection
  QI-019A Injection is an in vivo administered CAR-T gene therapy product that uses a lentiviral vector as the delivery system. Its mechanism of action involves transducing and integrating into the target T cell genome in the patient through the lentiviral vector, achieving stable expression of the CAR transgene, thereby generating CAR-T cells within the body.

Первичные конечные точки

• The number and severity of dose-limiting toxicity (DLT)events [Срок оценки: Within 28 Days After QI-019A infusion]
• The total number, incidence, and severity of Adverse Events(AEs) [Срок оценки: Within 28 Days After QI-019A infusion]

Вторичные конечные точки (8)

• Overall response rate (ORR） [Срок оценки: Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A]
• Complete response (CR) rate [Срок оценки: Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A.]
• Duration of response (DOR) [Срок оценки: Through study completion, an average of 2 year]
• Progression-free survival (PFS) [Срок оценки: up to 2 years after treatment of QI-019A.]
• Overall survival (OS) [Срок оценки: up to 2 years after treatment of QI-019A]
• Cmax [Срок оценки: Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A]
• Tmax [Срок оценки: Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A]
• AUC(0-day 28) [Срок оценки: Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28 after the treatment of QI-019A]

Критерии участия

Критерии включения

• 1\. Age ≥ 18 years, any gender;
• 2\. Diagnosed with multiple myeloma (MM) according to IMWG diagnostic criteria;
• 3\. Have received at least 2 lines of anti-MM treatment, with at least one full treatment cycle per line, and experienced disease progression during the most recent anti-myeloma treatment or within 12 months after it, confirmed by available clinical evidence; or deemed by the investigator to be refractory to both immunomodulatory agents and proteasome inhibitors, with disease progression during the most recent anti-myeloma treatment or within 2 months after it (according to IMWG diagnostic criteria);
• 4\. Disease must be measurable at screening, meeting one or more of the following criteria:

• Serum M protein level ≥ 0.5 g/dL;
• Or urine M protein level ≥ 200 mg/24h;
• Or involved serum free light chain ≥ 10 mg/dL with abnormal serum free light chain κ/λ ratio;
• 5\. ECOG performance status 0-2, with an expected survival of ≥ 3 months;
• 6\. Bone marrow function test results (from screening or within 2 months prior) meet the following requirements:

• Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week before screening), recombinant human erythropoietin allowed; for patients meeting the ≥ 6 g/dL hemoglobin requirement at screening, red blood cell transfusions are allowed to maintain hemoglobin ≥ 6 g/dL;
• Absolute neutrophil count (ANC) ≥ 600/μL (no use of granulocyte colony-stimulating factor (G-CSF) within 1 week before screening or pegylated G-CSF within 2 weeks before screening);
• Platelet count ≥ 50,000/μL;
• Lymphocyte count ≥ 500/μL;
• 7\. Normal renal function: Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥45 mL/min;
• 8\. Liver function must meet the following criteria:

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0× the upper limit of normal (ULN);
• Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤2.0× ULN (except for congenital hyperbilirubinemia, e.g., Gilbert's syndrome, direct bilirubin ≤1.5× ULN);
• Albumin ≥3 g/dL;
• 9\. Cardiac function must meet the following criteria:

• Left ventricular ejection fraction ≥50% (by echocardiography or MUGA scan);
• No clinically significant pericardial effusion;
• No clinically significant electrocardiogram abnormalities;
• 10\. Pulmonary function must meet the following criteria:

• Blood oxygen saturation ≥90% without oxygen supplementation;
• 11\. Women of childbearing potential must have a negative pregnancy test at screening and before drug infusion and must not be breastfeeding.
• 12\. Men and women of childbearing potential must agree to use effective contraception from the time of signing the informed consent until 1 year after the use of the study drug;
• 13\. Men and women of childbearing potential must agree not to donate sperm or eggs (oocytes) or other reproductive cells from the time of signing the informed consent until 1 year after the use of the study drug;
• 14\. The subject or their legal guardian agrees to participate in this clinical trial and signs the informed consent form (ICF), indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the study.

Критерии исключения

• 1.During screening, participants who have received other anticancer treatments (based mainly on investigator judgment):

• Received targeted therapy, epigenetic therapy, other investigational drugs, or treatment using invasive research medical devices within 5 half-lives;
• Received immune/non-immune-directed systemic therapy within 1 week;
• Received cytotoxic therapy within 2 weeks;
• Received proteasome inhibitors within 2 weeks;
• Received immunomodulatory therapy within 1 week.
• Received radiotherapy within 4 weeks (if the radiotherapy covered ≤5% of bone marrow reserve, the subject is eligible regardless of the radiotherapy end date);
• 2\. Received allogeneic hematopoietic stem cell transplantation within 6 months or autologous hematopoietic stem cell transplantation within 3 months before infusion;
• 3\. Had malignancies other than MM before screening, except for: malignancies treated with curative intent, with no known active disease ≥2 years prior to enrollment; or adequately treated non-melanoma skin cancer with no evidence of disease currently;
• 4\. Received any treatment using vesicular stomatitis virus G (VSVG) pseudotyped virus;
• 5\. Had severe, uncontrolled infection symptoms (bacterial, viral, fungal, etc.) during the screening period;
• 6\. Within 6 months before infusion, tested positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA levels above the normal range; tested positive for hepatitis C virus (HCV) antibody with peripheral blood HCV RNA levels above the normal range; tested positive for human immunodeficiency virus (HIV) antibody; or tested positive for syphilis;
• 7\. Had symptomatic heart failure or other serious cardiac diseases such as severe arrhythmias:

• New York Heart Association (NYHA) class III or IV congestive heart failure;
• Experienced myocardial infarction or underwent coronary artery bypass graft (CABG) or coronary stent implantation within 6 months prior to signing the ICF;
• Had clinically significant ventricular arrhythmias, or a history of unexplained syncope (excluding cases caused by vasovagal response or dehydration);
• Had a history of severe non-ischemic cardiomyopathy;
• 8\. Other clinically significant diseases, including:

• Primary immunodeficiency;
• Stroke or seizure within 6 months prior to screening;
• Clear clinical evidence of dementia or altered mental status;
• Parkinson's disease or Parkinsonian movement disorders or history thereof;
• 9\. Undergoing surgery within 2 weeks of administration or planned surgery within 2 weeks after administration, except for surgeries under local anesthesia;
• 10\. Administration of live attenuated vaccines within 1 month before dosing;
• 11\. Known severe allergic reaction to QI-019B or any of its formulation components;
• 12\. Known severe allergic reaction to tocilizumab;
• 13\. Unsuitable for establishing intravenous access;
• 14\. Other conditions deemed by the investigator to be unsuitable for participation in this study.

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 · 1 центр

• Union Hospital, Huazhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT07429721 · QH-WH-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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