此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

A Phase 1/2 Study of a Fully Human BCMA-targeting CAR (CT103A) in Patients With Relapsed/Refractory Multiple Myeloma (FUMANBA-1) (FUMANBA-1)

2021年11月21日 更新者：Nanjing IASO Biotherapeutics Co.,Ltd

Phase 1/2 Clinical Study on Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (CT103A) in the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

This study is a single-armed, open-label, multicenter Phase 1/2 study to evaluate the efficacy and safety of CT103A in subjects with relapsed and refractory MM.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

Leukapheresis procedure will be performed to manufacture CT103A chimeric antigen receptor (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of CT103A at 1.0 x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after CT103A infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after CT103A infusion.

研究类型

介入性

注册 (预期的)

132

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 中国
      • Beijing、中国
        • 招聘中
        • Peking University First Hospital
      • Beijing、中国
        • 招聘中
        • Beijing Boren Hospital
        • 接触：
          • Kai Hu
      • Chongqing、中国
        • 招聘中
        • Xinqiao Hospital, Army Medical University
      • Shanghai、中国
        • 招聘中
        • Fudan University Zhongshan Hospital
      • Shanghai、中国
        • 招聘中
        • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Tianjin、中国
        • 招聘中
        • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Anhui
      • Hefei、Anhui、中国
        • 招聘中
        • Anhui Provincial Cancer Hospital
    • Henan
      • Zhengzhou、Henan、中国
        • 招聘中
        • The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital
        • 接触：
          • Yongping Song
    • Hubei
      • Wuhan、Hubei、中国
        • 招聘中
        • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
        • 接触：
          • ChunRui Li
    • Hunan
      • Changsha、Hunan、中国
        • 招聘中
        • The third Xiangya Hospital of Central South University
    • Jiangsu
      • Nanjing、Jiangsu、中国
        • 招聘中
        • Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University
      • Nanjing、Jiangsu、中国
        • 招聘中
        • The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital
      • Xuzhou、Jiangsu、中国
        • 招聘中
        • The Affiliated Hospital of Xuzhou Medical University
    • Zhejiang
      • Hangzhou、Zhejiang、中国
        • 招聘中
        • The First Affiliated Hospital, Zhejiang University School of Medicine
        • 接触：
          • He Huang

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 70年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

Subjects must satisfy all the following criteria to be enrolled in the study:

  1. age 18 to 70 years old, male or female.
  2. Subjects with diagnosed relapsed or refractory MM according to IMWG criteria and have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Disease progression must be documented during or within 12 months following the most recent anti-myeloma treatment.
  3. 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).

  4. The subjects should have measurable disease based on at least one of the following parameters:

    • The proportion of primitive immature or monoclonal plasma cells detected by bone marrow cytology, bone marrow biopsy, or flow cytometry is ≥ 5%.
    • Serum M-protein ≥ 0.5 g/dL.
    • Urine M-protein ≥ 200 mg/24 hrs.
    • For those whose Serum or Urine M-protein does not meet the measurable criteria but the light chain type, serum free light chain (sFLC): involved sFLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
  5. ECOG performance score 0-1.
  6. Estimated life expectancy ≥ 12 weeks.

  7. Patients should have adequate organ function:

    • Hematology: Absolute neutrophil count (ANC) ≥1×10^9 /L (prior use of growth factor support is permitted, but subjects must not have received supportive treatment within 7 days prior to laboratory examination); absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L (subjects must not have received blood transfusion support within 7 days prior to laboratory examination); hemoglobin ≥60 g/L (subjects must not have received transfusion of red blood cells [RBC] within 7 days prior to laboratory examination; the use of recombinant human erythropoietin is permitted).
    • Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
    • Renal function: Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
    • Coagulation function: 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%.
  8. The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) for one year from the date of the subject's informed consent to the date of CAR T cell infusion.
  9. Subject must sign the informed consent form approved by ethics board in person before starting any screening procedure.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
  2. Subjects have received an autologous hematopoietic stem cell transplantation (auto-HSCT) within 12 weeks before leukapheresis or have a previous history of two times of allo-HSCT or previous history of an allogeneic hematopoietic stem cell transplantation (allo-HSCT).
  3. Insufficient mononuclear cells for CAR T cell production.
  4. Subjects have received any anti-cancer treatment as follows: targeted therapies, epigenetic therapy or invasive experimental instruments therapy within 14 days or at least 5 half-lives before leukapheresis (according to the longer time), or 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Subjects with a history of organ transplantation.
  10. Subjects have central nervous system (CNS) involvement (including cranial neuropathies or mass lesions and leptomeningeal disease).
  11. Subjects with extramedullary lesions (except for a single extramedullary lesion with a maximum transverse diameter of 3 cm).
  12. Subjects with plasma cell leukemia.
  13. 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).
  14. Subjects participated in another interventional clinical study 3 months before signing the informed consent (ICF);
  15. Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis collection (excluding < CTCAE grade 2 urogenital infection and upper respiratory infection).

  16. 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
  17. Pregnant or lactating women.
  18. Subjects with mental illness or consciousness disorder or disease of the central nervous system
  19. Subjects who haven't recovery to Grade 1 or baseline of any toxicities due to prior treatments, excluding alopecia.
  20. Other conditions that researchers consider inappropriate for inclusion.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：CT103A in relapsed and refractory multiple myeloma patients
CT103A autologous CAR-T cells will be infused at RP2D of 1.0 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy
药品：CT103A
CT103A 由用抗 BCMA CAR 慢病毒载体转导的自体 T 淋巴细胞组成，该载体含有独特的 CAR 结构和全人单链可变片段 (scFv)。

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Phase 1: Incidence and Severity of Adverse Events
大体时间：Minimum of 2 years post CT103A infusion
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Minimum of 2 years post CT103A infusion
Phase 1: Laboratoty tests
大体时间：Minimum of 2 years post CT103A infusion
Abnormal results of laboratoty tests
Minimum of 2 years post CT103A infusion
Phase 1: Vital signs
大体时间：Minimum of 2 years post CT103A infusion
Abnormal results of vital signs
Minimum of 2 years post CT103A infusion
Phase 1: Physical examination
大体时间：Minimum of 2 years post CT103A infusion
Abnormal results of physical examination
Minimum of 2 years post CT103A infusion
Phase 2: Overall response rate (ORR) evaluated by an Independent Review Committee (IRC)
大体时间：3 months post CT103A infusion
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC
3 months post CT103A infusion

次要结果测量

结果测量
措施说明
大体时间
Overall response rate (ORR) evaluated by the investigators
大体时间：3 months post CT103A infusion
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigators
3 months post CT103A infusion
Overall Survival (OS)
大体时间：Minimum of 2 years post CT103A infusion
Time from CT103A infusion to time of death due to any cause
Minimum of 2 years post CT103A infusion
Duration of Response (DOR)
大体时间：Minimum of 2 years post CT103A infusion
Time from first response evaluated by an IRC or investigators to disease progression or death from any cause
Minimum of 2 years post CT103A infusion
Progression-free Survival (PFS)
大体时间：Minimum of 2 years post CT103A infusion
Time from CT103A infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first
Minimum of 2 years post CT103A infusion
Time to Response (TTR)
大体时间：Minimum of 2 years post CT103A infusion
Time from CT103A infusion to first documentation of response evaluated by an IRC or investigators
Minimum of 2 years post CT103A infusion
Laboratoty tests
大体时间：Minimum of 2 years post CT103A infusion
Abnormal results of laboratoty tests
Minimum of 2 years post CT103A infusion
Vital signs
大体时间：Minimum of 2 years post CT103A infusion
Abnormal results of vital signs
Minimum of 2 years post CT103A infusion
Physical examination
大体时间：Minimum of 2 years post CT103A infusion
Abnormal results of physical examination
Minimum of 2 years post CT103A infusion
Minimal Residual Disease (MRD)
大体时间：Minimum of 2 years post CT103A infusion
Proportion of subjects who achieved MRD negative
Minimum of 2 years post CT103A infusion
Pharmacokinetics - Cmax
大体时间：Minimum of 2 years post CT103A infusion
The maximum transgene level at Tmax
Minimum of 2 years post CT103A infusion
Pharmacokinetics - Tmax
大体时间：Minimum of 2 years post CT103A infusion
Time to peak transgene level
Minimum of 2 years post CT103A infusion
Pharmacokinetics - AUC0-28days
大体时间：Minimum of 2 years post CT103A infusion
Area under the curve of CAR T cells from time zero to Day 28
Minimum of 2 years post CT103A infusion
Pharmacokinetics - AUC0-90days
大体时间：Minimum of 2 years post CT103A infusion
Area under the curve of CAR T cells from time zero to Day 90
Minimum of 2 years post CT103A infusion
soluble BCMA levels
大体时间：Minimum of 2 years post CT103A infusion
soluble BCMA levels in peripheral blood of subjects
Minimum of 2 years post CT103A infusion

其他结果措施

结果测量
措施说明
大体时间
Immunogenicity
大体时间：Minimum of 2 years post CT103A infusion
Development of an anti-CAR antibody response
Minimum of 2 years post CT103A infusion
replication competent lentivirus (RCL)
大体时间：Minimum of 2 years post CT103A infusion
The incidence of replication competent lentivirus (RCL)
Minimum of 2 years post CT103A infusion
the levels of CAR-T related inflammatory factors
大体时间：Minimum of 2 years post CT103A infusion
the levels of CRP, IL-6 and Ferritin
Minimum of 2 years post CT103A infusion

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Nanjing IASO Biotherapeutics Co.,Ltd

调查人员

  • 首席研究员：Lugui Qiu, MD, PhD、Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • 首席研究员：Chunrui Li, MD, PhD、Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2020年4月1日

初级完成 (预期的)

2022年10月1日

研究完成 (预期的)

2024年6月1日

研究注册日期

首次提交

2021年9月22日

首先提交符合 QC 标准的

2021年9月23日

首次发布 (实际的)

2021年10月4日

研究记录更新

最后更新发布 (实际的)

2021年11月23日

上次提交的符合 QC 标准的更新

2021年11月21日

最后验证

2021年9月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • XL-LCYJ-0007

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅