CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled:

* Subjects volunteer to participate in clinical trails, understand and inform the trials and sign informed consent form, be willing to complete all the trial procedures;
* 18 to 75 years old (including cut-off value), Male and female;
* Expected survival \> 12 weeks;
* Previously diagnosed as multiple myeloma by IMWG updated criteria (2014);
* One of the following indicators is satisfied:

  1. Serum M protein: for immunoglobulin G (IgG) type , M protein≥ 10 g/L, or for immunoglobulin A (IgA) type , M protein \> 5g/L, or for immunoglobulin D (IgD) type , M protein, IgD exceeds upper limit of normal range.
  2. Urine M protein ≥ 200 mg/24h;
  3. Serum free light chain ≥ 100 mg/L and Serum free light chain ratio is abnormal ;
* Patients with relapsed/refractory multiple myeloma. Relapsed is defined as: Patients have disease progression after at least three-line treatment regimens. Patients previously received at least 3 different mechanisms treatment regimens for multiple myeloma, including protease inhibitors and immunomodulators; Refractory is defined as: Patients who achieved minimal response(MR) or above was never achieved in previous treatment; MR or above was achieved in previous treatment, but disease progression occurred during subsequent treatment or within 60 days after the last treatment.
* ECOG score 0-2;
* Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Creatinine clearance (estimated by Cockcroft Gault formula) ≥ 40 mL/min;
  2. Left ventricular ejection fraction \>50%;
  3. Baseline peripheral oxygen saturation \>95%;
  4. Total bilirubin ≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
* The venous access required for collection can be established and leukepheresis can be carriedaccording to the judgement of investigators.

Exclusion Criteria:

Any one of the following conditions cannot be selected as a subject：

* Accompanied by other uncontrolled malignancies;
* Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood Hepatitis B virus(HBV) DNA titer is ≥500IU/mL; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus(HIV) antibody positive; syphilis primary screening antibody positive;
* Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure （New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
* Patients who are accounted to be not appropriate for this trail by investigator;
* Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
* Received CAR-T treatment or other gene therapies before enrollment;
* Those who failed to sign informed consent form or comply with the research procedures; Unwilling or unable to comply with research requirements;
* Have had severe immediate hypersensitivity reactions to any drugs used in this research;
* Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
* In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required;
* Patients with symptoms of central nervous system.

主要终点：Dose limited toxicity(DLT) · Safety Indicator · 28 days post infusion
次要终点：Pharmacokinetics parameters - Maximum CAR level in blood and CAR level in bone marrow(Cmax)；Pharmacokinetics parameters -Time to peak CAR level in blood (Tmax)；Pharmacokinetics parameters - 28-day Area under the curve of the CAR level in blood(AUC0-28)；Pharmacodynamics characteristics - Cytokines Concentrations,cytokines level in blood；Pharmacodynamics characteristics -Clonal bone marrow plasma cells level；Overall Response Rate (ORR) at 3 month post infusion；Percentage of Subjects With Negative Minimal Residual Disease (MRD)；Duration of Subjects With Negative Minimal Residual Disease (MRD)

• Human Derived anti-BCMA CAR-T Injection · EXPERIMENTAL · Single administration：1.0×10\^6 CAR+T, 3.0×10\^6 CAR+T, 6.0×10\^6 CAR+T

This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of Human Derived anti-BCMA CAR-T Injection , and to preliminarily observe the efficacy of the trial drug in patients with relapsed/refractory multiple myeloma.