Study to Evaluate the Safety of UF-KURE-BCMA CAR T-Cells in Advanced Myeloma

Other illness

• Disease-Specific Exclusions:
  • Active CNS involvement by multiple myeloma
  • Plasma cell leukemia
  • History of allogeneic hematopoietic stem cell transplantation
• Malignancy Exclusions:
  • o Second active malignancy, except: Non-melanoma skin cancer Carcinoma in situ (cervix, bladder, breast) Stage 1 uterine cancer Localized prostate cancer
• 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
• 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

Other

• Subjects meeting ANY of the following criteria will be excluded:
• Examples: rheumatoid arthritis, lupus

• Subjects must meet ALL of the following criteria to be eligible for study enrollment:
• Age: ≥18 years at time of signing informed consent
• 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)
• 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
• 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
• Performance Status: ECOG Performance Status 0-2 (see Appendix A)
• 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)
• 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
• Informed Consent: Ability to understand and willingness to provide written informed consent
• 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