Safety and Efficacy of Anti-BCMA-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM

Официальное название

A Clinical Study to Evaluate the Safety and Efficacy of BCMA-GPRC5D CAR-T in Patients With Relapsed/Refractory Multiple Myeloma Who Received Three or More Lines of Therapy

Обзор

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.

Подробное описание

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific BCMA-GPRC5D CAR-T cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.A leukapheresis procedure will be performed to manufacture Anti-BCMA-GPRC5D chimeric antigen receptor (CAR) modified T cells. Prior to Anti-BCMA-GPRC5D CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.

Вмешательства

• Биопрепарат Anti-BCMA-GPRC5D CAR-T cells infusion
  Subiects who meet the enrollment conditions will receive intravenous infusion of anti-BCMA-GPRC5D CAR-T Cells after lymphodepleting therapy.

Первичные конечные точки

• Incidence of adverse events(AE) after infusion [Срок оценки: within 2 years after infusion]

Вторичные конечные точки (4)

• Overall Response Rate (ORR) [Срок оценки: within 2 years after infusion]
• Concentration of CAR-T cells [Срок оценки: Days 1,4, 7, 10, 14 ,21,28and months 2, 3, 6, 9, 12,18,24 after infusion]
• Progression-free survival(PFS) [Срок оценки: within 2 years after infusion]
• Overall survival(OS) [Срок оценки: within 2 years after infusion]

Критерии участия

Критерии включения

• The patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure;
• Age 18-75 years old, gender unlimited;
• Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG);
• The presence of measurable disease at screening meets one of the following criteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed as Light-chain MM without measurable disease in serum and urine; Serum free light chain ≥ 10 mg/dL with an abnormal κ/λ ratio;
• Patients must relapse or be refractory after three or more lines of therapy, which at least include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), and one anti-CD38 monoclonal antibody;
• diagnosed as relapsed/refractory disease or primary refractory disease;
• The last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy;
• The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade < 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy);
• ECOG score 1-2 points and the expected survival period ≥ 3 months;
• Liver, kidney and cardiopulmonary functions meet the following requirements:

• Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN;
• Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min;
• Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days;
• Baseline peripheral oxygen saturation > 92%;
• Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic) calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);
• Left ventricular ejection fraction (LVEF) > 45%, without confirmed pericardiac effusion and abnormal electrocardiography with clinical significance;
• Without clinically significant pleural effusion;
• Venous access could be established; without contraindications of apheresis.

Критерии исключения

• Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma;
• Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter;
• It is suspected that MM has involved the central nervous system or meninges and has been confirmed by MRI or CT, or there are other active central nervous system diseases;
• Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL, amyloidosis;
• Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution;
• Patients have a severe allergic history;
• Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure \[New York Heart Association (NYHA) classification ≥ grade III\];
• Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
• Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening;
• Active autoimmune or inflammatory diseases of the nervous system;
• Patients develop oncology emergencies and need to be treated before screening or infusion;
• Uncontrolled infections that need antibiotics treatment;
• Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;
• Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis;
• Patients receive a major surgical operation within 4 weeks before lymphodepletion or do not recover completely before the enrollment; or plan to receive a major surgical operation during the study period;
• Live attenuated vaccine within 4 weeks before screening;
• Persons with serious mental illness;
• Alcoholics or persons with a history of drug abuse;
• Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion;
• Any unsuitable to participate in this trial judged 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 · 1 центр

• Sanbin Wang — Куньмин

Идентификаторы

NCT: NCT06515262 · BG-CT-23-015

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗