Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of R/RMM

Официальное название

A Multicenter Clinical Study on the Safety and Efficacy of Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of Relapsed/Refractory Multiple Myeloma

Обзор

To explore the safety and efficacy of nanobody-based BCMA-targeting biepitope CAR-T cells in the treatment of relapsed/refractory multiple myeloma，this study will be conducted in multiple study centers, with 60 patients openly enrolled to receive CAR-T cell therapy. Patients participating in clinical trials will be tested and evaluated for treatment safety, efficacy, duration of response, and long-term survival.

Подробное описание

This study is a multicenter, open-label, prospective, single-arm clinical study with patients with relapsed/refractory multiple myeloma as the test subjects, in order to evaluate the safety and efficacy of nanobody-based biepitope CAR-T cells targeting BCMA in the treatment of R/RMM, and to collect CAR-T PK/PD indicators. The structure of BCMA target CAR-T is designed to identify two different epitopes of BCMA protein with two recognition domains, in order to killig MM cells without secreting more pro-inflammatory factors and avoiding escape caused by the limitations of single BCMA antigen recognition.

Вмешательства

• Препарат Nanobody-based biepitope BCMA-targeting CAR-T cells
  Each patient will receive nanobody-based biepitope BCMA-targeting CAR-T cell by intravenous infusion on day 0.

Первичные конечные точки

• Incidence of Treatment-related Adverse Events [Срок оценки: within 3 years after infusion]
• Overall response rate (ORR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM [Срок оценки: within 3 years after infusion]
• The rates of complete response (CR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM [Срок оценки: within 3 years after infusion]
• Very good partial response (VGPR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM [Срок оценки: within 3 years after infusion]
• Partial response rate (PR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM [Срок оценки: within 3 years after infusion]
• Stable diseases (SD) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM [Срок оценки: within 3 years after infusion]

Вторичные конечные точки (3)

• Overall survival (OS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma [Срок оценки: within 3 years after infusion]
• Progression-free survival (PFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma [Срок оценки: within 3 years after infusion]
• Event-free survival (EFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma [Срок оценки: within 3 years after infusion]

Критерии участия

Критерии включения

• Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
• Aged ≥ 18 years and ≤ 75 years.
• Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG 2014).
• Diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve MR or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment.
• Flow cytometry or immunohistochemistry showed positive BCMA expression in myeloma cells.
• Have not been treated with antibody-based drugs within 2 weeks prior to cell therapy.
• ECOG score 0-2 points.
• HGB≥70g/L，PLT≥30×10\^9/L.
• Liver, kidney and cardiopulmonary functions meet the following requirements:

• Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) >30 ml/min；
• Left ventricular ejection fraction (LVEF) ≥50%,
• Baseline peripheral oxygen saturation > 90%;
• Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

Критерии исключения

• Previous diagnosis and treatment of other malignancies within 3 years;
• Presence of one of the following cardiac criteria: atrial fibrillation; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary QT prolongation, as judged by the investigator. Echocardiogram LVSF <30% or LVEF <50%; Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New York Heart Association) III or IV (absence of this symptom confirmed by echocardiography within 12 months of treatment);
• Patients with active GVHD;
• Patients with a history of severe pulmonary impairment disease;
• Combined with other malignant tumors in the advanced stage;
• Co-infection with severe or persistent infection that cannot be effectively controlled;
• Combined with severe autoimmune disease or congenital immunodeficiency;
• Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA ≥ 500 IU/ml and abnormal liver function\] or hepatitis C antibody \[HCV-Ab\] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function);
• Human immunodeficiency virus (HIV) infection or syphilis infection;
• Patients with a history of severe allergy to biological products (including antibiotics);
• Patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;
• Pregnant or Lactating Women; Patients and his or her spouses have a fertility plan within 12 months after CAR-T cell infusion;
• Other conditions considered inappropriate by the researcher.

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, Tongji Medical College, Huazhong University of Science and Technology — Ухань

Публикации

• Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, Vogl DT, Weiss BM, Dengel K, Nelson A, Plesa G, Chen F, Davis MM, Hwang WT, Young RM, Brogdon JL, Isaacs R, Pruteanu-Malinici I, Siegel DL, Levine BL, June CH, Milone MC. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019 Mar 21;129(6):2210-2221. doi: 10.1172/JCI126 PMID 30896447
• Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O'Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S. Ciltacabtagene a PMID 34175021
• Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517- PMID 25319501
• Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, Brudno JN, Stetler-Stevenson M, Feldman SA, Hansen BG, Fellowes VS, Hakim FT, Gress RE, Kochenderfer JN. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016 Sep 29;128(13):1688-700. doi: 10.1182/blood-2016-04-711903. Epub 2016 Jul 13. PMID 27412889

Идентификаторы

NCT: NCT06503107 · biepitope BCMA CAR-T

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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