CD19-BCMA Dual Nanobody Based CAR-T Cells for Patients With DSA

Официальное название

Clinical Trial of CD19-BCMA Dual Nanobody Based CAR-T Cells for Patients With Donor-specific Antibodies

Обзор

This is an early-stage, open-label clinical study of CD19-BCMA dual nanobody based CAR-T Cell desensitization therapy for patients positive for Donor-Specific Antibodies. Enrolled subjects will participate in an early clinical study using the traditional "3+3" dose escalation design to determine the Maximum Tolerated Dose (MTD) of CAR-T cell infusion (i.e., three escalating dose levels: 0.5x10\^6 CAR+ T cells/kg, 1x10\^6 CAR+ T cells/kg, 2x10\^6 CAR+ T cells/kg). The investigators and the sponsor will jointly form a Safety Review Committee (SRC). The final decision on whether to continue increasing the dose levels or to conduct an expansion study at a specific dose level will be based on the safety and efficacy data obtained from the three dose groups. Assessments will be performed every 4 weeks after cell infusion, with a total planned enrollment of 9-18 subjects.

Вмешательства

• Биопрепарат CD19-BCMA dual nanobody based CAR-T Cells
  Desensitization

Первичные конечные точки

• • Incidence and severity of AEs and SAEs within 1 month after cell infusion [Срок оценки: From enrollment to the end of treatment at 4-5 weeks]
• • Incidence and severity of ICANS [Срок оценки: From enrollment to the end of treatment at 4-5 weeks]
• Incidence and severity of ICAHT [Срок оценки: From enrollment to the end of treatment at 4-5 weeks]

Вторичные конечные точки (1)

• DSA seroconversion rate (≤ 2000 MFI) at 3 months post-infusion [Срок оценки: From enrollment to the end of treatment at 12 weeks]

Критерии участия

Критерии включения

• The subject or their legal guardian understands and voluntarily signs the Informed Consent Form (ICF).
• Male or female, aged 3 years or older (inclusive) at the time of signing the ICF.
• Expected survival period is not less than 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 at the time of signing the ICF.
• At the time of signing the ICF, the following must be satisfied:

• Meets the indications for allogeneic hematopoietic stem cell transplantation, is at a suitable stage for transplantation, and is planned to receive a haploidentical related donor allogeneic hematopoietic stem cell transplant.
• The patient has no available HLA-matched sibling donor, no other HLA-matched unrelated donor, and no related donor who is DSA-negative.
• The patient has a DSA level ≥5000 MFI.
• Major organ function must meet the following requirements:

• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 5 × Upper Limit of Normal (ULN).
• Total bilirubin ≤ 2 × ULN.
• For adult subjects: Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula) OR Serum creatinine ≤ 1.5 × ULN.
• For pediatric subjects: Serum creatinine must not exceed: 1.2 mg/dL for ages 12-13; 1.5 mg/dL for males aged 13-16; 1.4 mg/dL for females aged >13; 1.7 mg/dL for males aged >16.
• HBV-DNA, HCV-RNA, Syphilis antibody, HIV antibody, CMV/EBV DNA must be negative; no active infection.
• Oxygen saturation > 92%.
• Men and women of childbearing potential must agree to use effective contraception from the time of signing the ICF until 2 years after administration of the study drug. Women of childbearing potential include premenopausal women and women within 2 years of menopause. A negative blood pregnancy test is required for women of childbearing potential at screening.

Критерии исключения

• History of central nervous system (CNS) diseases, including but not limited to epilepsy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, neuropathy. Subjects with a history of conditions like lacunar infarction without related neurological symptoms before screening may be considered for exclusion based on the investigator's judgment.
• Other severe, progressive, or uncontrolled gastrointestinal, urinary, endocrine, or respiratory diseases, deemed by the investigator as unsuitable for enrollment.
• Participation in another clinical trial within 2 weeks prior to screening.
• Other factors that may influence DSA levels: Received proteasome inhibitors or BTK inhibitors, rituximab, or other monoclonal antibodies targeting B cells or plasma cells (e.g., belimumab, telitacicept, daratumumab) within 2 weeks prior to signing the ICF.
• Presence of any uncontrolled active infection at the time of signing the ICF or within 4 weeks prior to leukapheresis.
• Positive HBsAg or positive HBcAb with detectable HBV DNA at screening; Positive HCV antibody with detectable HCV RNA at screening; Positive HIV antibody; Positive CMV DNA; Positive EBV DNA; Positive for both treponemal and non-treponemal syphilis antibodies.
• Clinically significant cardiovascular diseases, including any of the following:

• QTc interval ≥ 480 ms (corrected using Fridericia's formula).
• New York Heart Association (NYHA) Class II or higher heart failure.
• Unstable angina or acute myocardial infarction within 6 months prior to signing the ICF.
• Left Ventricular Ejection Fraction (LVEF) < 50%.
• Poorly controlled hypertension (judged by the investigator based on the subject's individual condition).
• Clinically significant arrhythmias requiring antiarrhythmic treatment (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, complete left bundle branch block, etc.).
• Allergy to any component of the drugs used in this study.
• Received large-field radiotherapy within 4 weeks prior to signing the ICF, except for palliative radiotherapy for non-target lesions during the study period.
• Requirement for systemic corticosteroids (at a dose equivalent to or higher than prednisone 10 mg/day) or other immunosuppressive drugs within 3 days prior to leukapheresis or anticipated during the study period, except for the following:

• Nasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular).
• Systemic corticosteroid therapy not exceeding prednisone 10 mg/day or an equivalent physiological dose.
• Steroids used as premedication for allergic reactions (e.g., pre-CT scan).
• Used for managing adverse reactions post-infusion.
• Major surgical procedure within 4 weeks prior to signing the ICF (excluding routine biopsy surgery), or anticipated major surgery during the study period.
• History of active tuberculosis infection within 1 year prior to signing the ICF (subjects with a history of active tuberculosis more than 1 year ago may be included if the investigator judges there is no current evidence of active tuberculosis).
• Administration of live/attenuated or inactivated vaccines within 4 weeks prior to signing the ICF, or planned administration during the screening period.
• Pregnant or lactating women.
• Men or women who refuse to use contraception from the time of signing the ICF until 12 months after study completion.
• History of alcohol abuse, drug abuse, or psychiatric history.
• Any comorbidities or other conditions that, in the investigator's opinion, may affect protocol compliance or make the subject unsuitable for participation.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07451236 · 2025PHD029

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗