New CAR T-Cell therapy targets Hard-to-Treat myeloma

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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