Phase I Clinical Study of a Fully Human BCMA-targeting CAR (CT103A) Combined With Selinexor in the Treatment of Patients With Relapsed/Refractory Extramedullary Multiple Myeloma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This study is a single-center, open Phase I study, to observe the effectiveness and safety of CT103A combined with different doses of Selinexor in patients with relapsed/refractory extramedullary multiple myeloma, and the pharmacokinetics of Selinexor and CT103A Kinetic and pharmacodynamic characteristics.
详细描述
In this study, two dose groups of 20 mg/week and 40 mg/week will be set for Selinexor, and the dose of CT103A is 1.0×106 cells/Kg. Subjects in all dose groups will firstly receive a single dose infusion of CT103A, at least 1 month post infusion and platelet recovery to ≥50×109/L. Then subjects began to take Selinexor once a week for one year. Each dose group level will include 8-10 subjects, and a total of 16-20 subjects are expected to be enrolled.
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
- •Subjects must satisfy all the following criteria to be enrolled in the study:
- •age ≥18 years old, male or female.
- •Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 3 prior lines of therapy
- •Evidence of cell membrane BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue(e.g., bone marrow biopsies, or plasmacytoma).
- •Subjects with extramedullary myeloma require extramedullary lesions with a maximum diameter of ≥2cm
- •ECOG score is ≤ 2
- •Estimated life expectancy ≥ 12 weeks.
- •Subjects should have adequate organ function:
- •Absolute neutrophil count (ANC) ≥1×10^9 /L; absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L; hemoglobin ≥60 g/L.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
- •Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
- •Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤1.5×ULN.
- •SpO2 > 91%.
- •Left ventricular ejection fraction (LVEF) ≥ 50%.
- •The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) from the date of the subject's informed consent to one year post CAR T cell infusion.
- •Subject must sign the informed consent form approved by the ethics board in person before starting any screening procedure.
排除标准
- •The presence of any of the following will exclude a subject from enrollment:
- •Subjects who are known to be resistant to Selinexor;
- •Subjects who need to use immunosuppressive agents for a long time due to graft-versus-host disease (GVHD) or autoimmune diseases.
- •Subjects have received any anti-cancer treatment as follows: monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis, or anti-tumor treatments other than those listed above within 30 days before leukapheresis.
- •Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use.
- •Subjects with hypertension that cannot be controlled by medication
- •Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
- •Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment.
- •Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery.
- •Subjects with a history of organ transplantation.
- •Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia)
- •Subjects participated in another interventional clinical study within 1 month before signing the informed consent (ICF).
- •Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis.
- •Positive for any of the following tests:
- •Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood
- •Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood
- •Human immunodeficiency virus (HIV) antibody
- •Cytomegalovirus (CMV) DNA
- •Treponema Pallidum antibody
- •Pregnant or lactating women.
- •Subjects with mental illness or consciousness disorder or disease of the central nervous system
- •Other conditions that researchers consider inappropriate for enrollment.
研究组 & 干预措施
CT103A combined with Selinexor
All subjects will be assigned to two Selinexor dose groups of 20 mg/week and 40 mg/week after receiving a single dose infusion of CT103A.
干预措施: Selinexor (Drug)
CT103A combined with Selinexor
All subjects will be assigned to two Selinexor dose groups of 20 mg/week and 40 mg/week after receiving a single dose infusion of CT103A.
干预措施: CT103A (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 1 year post CT103A infusion
The time from the start of CT103A treatment for the subjects to the first disease progression or death for any reason.
Objective response rate (ORR)
时间窗: 1 year post CT103A infusion
The percentage of subjects who achieved sCR、CR、VGPR、PR.
Duration of response (DOR) after administration
时间窗: 1 year post CT103A infusion
DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria
次要结局
- Pharmacokinetics - Tmax of CT103A(1 year post CT103A infusion)
- Pharmacokinetics - AUC0-28days of CT103A(1 year post CT103A infusion)
- Health-related quality of life assessment(1 year post CT103A infusion)
- Overall survival (OS)(1 year post CT103A infusion)
- Minimal Residual Disease (MRD) efficacy evaluation(1 year post CT103A infusion)
- Pharmacokinetics - Cmax of CT103A(1 year post CT103A infusion)
- Concentration of immunoglobulins(1 year post CAR-T cell infusion)
- Pharmacokinetics - AUC0-90days of CT103A(1 year post CT103A infusion)
- Evaluation of lymphocyte subsets(1 year post CAR-T cell infusion)
- Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group(1 year post CT103A infusion)
- Pharmacokinetics of Selinexor(1 year post CT103A infusion)
- PD endpoints(1 year post CT103A infusion)
- Appraisal of life quality(1 year post CAR-T cell infusion)
研究者
Chunrui Li
Professor
Tongji Hospital