A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 5
- 主要终点
- Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period
研究概览
简要总结
The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.
详细描述
The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane activator and calcium modulator and cyclophilin ligand interactor). Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously as a single or split dose and will then enter a 12-month follow-up period.
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 patients, aged ≥
- •Willing and able to give written, informed consent.
- •Confirmed diagnosis of MM.
- •Measurable disease as defined by IMWG.
- •Relapse or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, alkylator and immunomodulatory therapy (IMiD), or have "double refractory" disease to a proteasome inhibitor and IMiD.
- •For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening and confirmed before receiving study treatment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to
- •Peripheral blood total lymphocyte count > 0.5 x 10⁹/L.
排除标准
- •Women who are pregnant or lactating.
- •Prior treatment with investigational or approved gene therapy or cell therapy products.
- •Patient has previously received an allogenic stem cell transplant.
- •Clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event.
- •Left Ventricular Ejection fraction < 50 unless the institutional lower limit of normal is lower.
- •Significant liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × ULN, or total bilirubin > 2.0 mg/dL or evidence of end stage liver disease (e.g. ascites, hepatic encephalopathy).
- •Chronic renal impairment requiring dialysis, or calculated creatinine clearance < 30 mL/min
- •Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatmenUse of rituximab within the last 3 months.
- •Active autoimmune disease requiring immunosuppression.
- •Received any anti-myeloma therapy within the last 21 days prior to preconditioning or 10 days prior to leukapheresis; steroids of up to 160 mg of dexamethasone are permitted so long as > 7 days post-dose prior to pre-conditioning or leukapheresis.
- •Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.
结局指标
主要结局
Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period
时间窗: Up to 28 days post-infusion
Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)
时间窗: Up to 28 days post-infusion
Dose limiting toxicity was defined as: Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.
Number of Infused Patients With Best Overall Response
时间窗: Up to 2 years
Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations
次要结局
- Overall Survival(Up to 2 years)
- Duration of Response(Up to 2 years)
- Time to Disease Progression(Up to 2 years)
- Proportion of Patients for Whom an AUTO2 Product Can be Generated(Up to 2 years)
- Clinical Benefit Rate(Up to 2 years)
- Progression-free Survival(Up to 2 years)
- Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood(Up to 2 years)