CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

Subjects must meet ALL of the following criteria to be eligible for study enrollment:

1. Age: ≥18 years at time of signing informed consent
2. Diagnosis: Documented multiple myeloma meeting one of the following:

   * Relapsed disease: Progression after achieving at least minimal response (MR) to prior therapy
   * Refractory disease: Non-responsive or progressive disease while on therapy or within 60 days of last treatment (in subjects who achieved ≥MR on prior therapy)
3. Prior Therapy:

   * Received ≥3 prior lines of anti-myeloma therapy
   * Prior therapy must include:

   At least one proteasome inhibitor At least one immunomodulatory drug (e.g., lenalidomide, pomalidomide, thalidomide) At least one anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab) o Prior anti-BCMA CAR-T therapy is permitted if subject achieved PFS ≥6 months post-infusion
4. Measurable Disease: At least one of the following at screening (for response assessment eligibility):

   * Serum M-protein ≥0.5 g/dL by protein electrophoresis (SPEP)
   * Urine M-protein ≥200 mg/24 hours by protein electrophoresis (UPEP)
   * Serum free light chain (FLC) difference ≥10 mg/dL with abnormal FLC ratio Note: Subjects with non-measurable disease may enroll for safety assessment
5. Performance Status: ECOG Performance Status 0-2 (see Appendix A)
6. Organ Function: Adequate organ function as defined by:

   Hepatic:

   o Total bilirubin ≤2× institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome
   * AST and ALT ≤2.5× institutional ULN

   Renal:

   o Calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault formula)

   Cardiac:

   o Left ventricular ejection fraction (LVEF) ≥45% by echocardiogram or MUGA

   Pulmonary:

   o ≤Grade 1 dyspnea

   o Oxygen saturation ≥92% on room air

   o If PFTs performed: FEV₁ ≥50% predicted and DLCO ≥40% predicted (corrected for hemoglobin)
7. Prior Therapy Washout:

   o ≥2 weeks since last radiation or systemic anti-myeloma therapy (standard agents)

   o ≥4 weeks since last investigational therapy

   o ≥6 weeks since autologous stem cell transplant
8. Informed Consent: Ability to understand and willingness to provide written informed consent
9. Contraception Requirements (for subjects of reproductive potential):

Female subjects:

o Women of childbearing potential must: Have negative serum pregnancy test at screening Agree to use highly effective contraception (failure rate \<1% per year) from enrollment through 6 months post-CAR-T infusion

* Acceptable methods: bilateral tubal ligation, male partner sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing IUD, copper IUD
* Sexual abstinence is acceptable if consistent with subject's preferred lifestyle

Male subjects:

* Must agree to use condom plus effective contraception if partner is of childbearing potential
* Must refrain from sperm donation from enrollment through 6 months post-CAR-T infusion

Exclusion Criteria:

Subjects meeting ANY of the following criteria will be excluded:

1. Disease-Specific Exclusions:

   * Active CNS involvement by multiple myeloma
   * Plasma cell leukemia
   * History of allogeneic hematopoietic stem cell transplantation
2. Malignancy Exclusions:

   o Second active malignancy, except: Non-melanoma skin cancer Carcinoma in situ (cervix, bladder, breast) Stage 1 uterine cancer Localized prostate cancer
3. Cardiovascular Exclusions:

   * New York Heart Association (NYHA) Class IV congestive heart failure
   * Unstable angina pectoris
   * Clinically significant cardiac arrhythmias
   * Myocardial infarction, stroke, or TIA within 6 months of enrollment
4. Infectious Disease Exclusions:

   * Known HIV infection or AIDS-related illness
   * Active hepatitis B or C infection:

Positive HBsAg, or Positive anti-HBc or anti-HCV with detectable viral nucleic acid by PCR

* Active infection requiring systemic therapy 5. Neurological Exclusions:
* History of clinically relevant CNS pathology including:

Epilepsy or seizure disorders Paresis, aphasia Uncontrolled cerebrovascular disease Severe brain injury Dementia Parkinson's disease 6. Autoimmune Disease:

* Active autoimmune disease requiring systemic immunosuppression \>15 mg/day prednisone equivalent within past 6 months
* Examples: rheumatoid arthritis, lupus

主要终点：Incidence of dose-limiting toxicities (DLT occurring within 28 days of CAR-T cell infusion) · DLT · Within 28 days of CAR-T cell infusion
次要终点：Manufacturing success rate；Treatment-emergent adverse events；ORR per IMWG criteria；DOR；PFS；OS

• Lower Dose Level · ACTIVE_COMPARATOR · Lower Dose (Level -1): 3 × 10⁶ cells (≥50 kg)// 2 × 10⁶ cells (\<50 kg)
• Starting Dose Level · ACTIVE_COMPARATOR · Starting Dose Level (Level 1) : 10 × 10⁶ cells (≥50 kg) / 7 × 10⁶ cells (\<50 kg)
• Higher Dose Level · ACTIVE_COMPARATOR · Higher Dose Level (Level 2): 15 × 10⁶ cells (≥50 kg) / 10 × 10⁶ cells (\<50 kg)

The goal of this study is to evaluate the safety of a new type of CAR T-cell, UF-KURE-BCMA, for the treatment of patients with advanced multiple myeloma that has not responded to other therapies. The main question is whether the use of these new CAR T-cells is safe for patients with this condition. Secondarily, the study will also look at the response of myeloma to this therapy.