Phase I/II Open-label Study Evaluating The Safety And Efficacy of Anti BCMA CAR-T Cell Therapy in Adults With R/ R Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Phase I. Safety
研究概览
简要总结
The mail purpose of this study is to estimate the safety and the efficacy of anti-BCMA CAR- T cell immunotherapy for adults with relapsed or refractory multiple myeloma
详细描述
Locally manufactured second generation autologous humanized anti-BCMA cells are used for immunotherapy. Protocol treatment includes leukapheresis in order to harvest T cells, lymphodepleting conditioning (fludarabine 30 mg/m2+ cyclophosphamide 300 mg/2(days -5-3)) followed by one anti (day 0) BCMA CAR-T cell infusion.
The Main research objectives of the Phase I:
To preliminarily explore the safety (incidence of CRS, ICANS, HLH, infections, late ICAHT, p arkinsonism and cytopenias) and tolerability.
The Secondary research objectives of the Phase I:
To explore the pharmacokinetics of CAR-T cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥18 years.
- •Willing and able to give written, informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to
- •Relapsed or refractory multiple myeloma according to IMWG criteria with two previous lines of therapy and resistance to proteosome inhibitors and immunomodulators.
- •Adequate organ system function including
- •- Creatinine clearance ≥30 cc/min.
- •- Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x upper limit of normal (ULN).
- •- Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome.
- •- Left ventricular ejection fraction (LVEF) ≥50% (by echocardiogram [ECHO] or
- •- Baseline oxygen saturation >92% on room air and ≤Grade 1 dyspnoea.
- •Have no active GVHD (Grade 2-4)
- •Adequate bone marrow (BM) function
- •Absolute neutrophil count ≥1.0 × 10^9/L.
- •Absolute lymphocyte count ≥0.3 × 10^9/L (at enrolment and prior to leukapheresis).
- •Haemoglobin ≥80 g/L.
- •Platelets ≥50 × 10^9/L
排除标准
- •Females who are pregnant or lactating.
- •History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
- •Patients with active CNS involvement by malignancy. Patients with history of central nervous system (CNS) involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to CAR-T infusion).
- •Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event.
- •Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis.
- •History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months.
- •6. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis.
- •7. History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed).
- •8. The following medications are excluded:
- •Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to CAR-T administration. However, physiological replacement, topical, and inhaled steroids are permitted.
- •Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or CAR-T cells infusion.
- •Cytotoxic chemotherapies within 1 week of CAR-T cellsinfusion and 1 week prior to leukapheresis.
- •Granulocyte-colony stimulating factor less than 14 days prior to leukapheresis.
- •Live vaccine ≤4 weeks prior to enrolment.
- •Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy.
- •Prior limited radiation therapy within 2 weeks of CAR-T cells infusion.
- •Prior anti BCMA therapy
- •Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine or tocilizumab.
- •11. Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial.
研究组 & 干预措施
anti BCMA CAR-T cell-immunotherapy
干预措施: anti BCMA CAR-T cells (Biological)
结局指标
主要结局
Phase I. Safety
时间窗: 1 month post CAR-T cells infusion
Number of Participants With Grade 3-5 Toxicities. Adverse events will be graded according to the CTCAE v5.0, ICAHT and ASCTC.
Phase II. Overall response rate
时间窗: 12 months post CAR-T cells infusion
partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR) rates according to IMVG criteria
次要结局
- Phase I. duration of expansion of CAR-T cells(12 months post CAR-T cells infusion)
- Phase II. Efficacy: Overall survival rates(3 years post CAR-T cells infusion)
- Phase II. Progression-free survival rates(3 years post CAR-T cells infusion)
- Phase II. Duration of response(3 years post CAR-T cells infusion)
- Phase I. Peak of expansion of CAR-T cells(1 month post CAR-T cells infusion)
研究者
Mikhail Uss
Dr. Mikhail Uss. Head of the Department of Bone Marrow Transplantation, Researcher
Minsk Scientific-Practical Center for Surgery, Transplantation and Hematology