CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Able and willing to provide written informed consent and comply with the scheduled visits, study treatment, laboratory assessments, and other study procedures.
2. Clinically diagnosed relapsed or refractory multiple myeloma or plasma cell leukemia (PCL). Patients with persistent minimal residual disease (MRD) positivity or conversion from MRD-negative to MRD-positive status following induction and consolidation therapy are also eligible for enrollment.
3. Age 18 to 80 years, inclusive.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
5. Estimated life expectancy \> 3 months from the date of signing the informed consent form.
6. Hemoglobin ≥ 60 g/L (transfusion permitted).
7. Adequate organ function as defined below:

   * Creatinine clearance (CrCl) ≥ 40 mL/min, calculated using the Cockcroft-Gault formula;
   * Left ventricular ejection fraction (LVEF) ≥ 50%;
   * Oxygen saturation \> 90% on room air;
   * Total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
8. Participants of childbearing potential must agree to use effective contraception prior to study enrollment and for at least 6 months after completion of study treatment. Participants who become pregnant or suspect pregnancy must notify the investigator immediately.

Exclusion Criteria:

1. History within 1 year prior to signing the informed consent form of any of the following:

   * New York Heart Association (NYHA) Class III or IV heart failure;
   * Myocardial infarction;
   * Cardiac angioplasty or stent placement;
   * Unstable angina;
   * Other clinically significant symptomatic cardiac disease;
2. Active graft-versus-host disease (GVHD) or requirement for systemic immunosuppressive therapy.
3. History of other malignancies within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, or ductal carcinoma in situ of the breast after curative surgery.
4. Active infection requiring systemic therapy or uncontrolled infection within 7 days prior to screening (excluding mild genitourinary or upper respiratory tract infections).
5. Evidence of active viral or infectious disease as follows:

   * Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA above the lower limit of detection;
   * Positive hepatitis C virus (HCV) antibody with detectable HCV RNA;
   * Positive human immunodeficiency virus (HIV) antibody;
   * Positive Treponema pallidum particle agglutination assay (TPPA).
6. Participation in another clinical trial within 4 weeks prior to signing the informed consent form, or if the time from the last dose of an investigational drug to informed consent is less than 5 half-lives of that drug (whichever is longer).
7. History of severe allergic reactions to biologic products.
8. Any unstable systemic disease, as judged by the investigator, including but not limited to severe hepatic, renal, or metabolic disorders requiring medical treatment.
9. Pregnant or breastfeeding women; women planning to become pregnant within 2 years after cell infusion; or male participants whose partners plan to become pregnant within 2 years after cell infusion.
10. Any condition that, in the opinion of the investigator, may increase the participant's risk or interfere with study participation or interpretation of study results.

主要终点：Overall response rate (ORR) · Percentage of participants with presence of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). ORR assessment will be based on International Myeloma Working Group (IMWG) response criteria. · From infusion to 12 months
次要终点：Complete Response Rate；MRD-negative rate；CR/MRD-negative rate；Time to Response；Duration of Response (DOR)；Progression-free survival (PFS)；Overall Survival (OS)；Cmax

• IL-15 armored CAR-T cells · EXPERIMENTAL · Bridging therapy is permitted at the investigator's discretion. Radiotherapy is permitted before infusion for subjects with extramedullary disease. Lymphodepletion with fludarabine plus cyclophosphamide will be performed prior to CAR-T cells infusion.

This is an open-label, single-arm, Phase 2 study to evaluate the efficacy and safety of IL-15-armored chimeric antigen receptor T-cell (CAR-T) therapy in subjects with relapsed or refractory multiple myeloma and plasma cell leukemia.