RN1201 Injection in Newly Diagnosed High-Risk Cytogenetic Multiple Myeloma

Korábbi kezelés

• A subject will not be eligible for this trial if any of the following criteria are met:
  • Known history of allergic reaction, hypersensitivity, intolerance, or contraindication to the BCMA/CD19 allogeneic CAR-T product or any of its excipients, including fludarabine, cyclophosphamide, and tocilizumab.
  • Diagnosis of plasma cell leukemia.
  • Presence of non-paraskeletal extramedullary disease.
  • Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with active graft-versus-host disease (GVHD) that requires treatment with steroids or immunosuppressive agents.
  • Presence of a severe, active infection, including:
  • Human Immunodeficiency Virus (HIV) infection (subjects must have a negative HIV 1/2 antibody screen).
  • Hepatitis C Virus (HCV) infection (subjects must have a negative anti-HCV antibody screen).
  • Hepatitis B Virus (HBV) infection (subjects must have a negative HBsAg screen).
  • History of prior gene therapy or genetically modified cell immunotherapy.
  • Active autoimmune disease, including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease, or multiple sclerosis; or a history of a severe autoimmune disease (as judged by the Principal Investigator) that required long-term immunosuppressive therapy.
  • Diagnosis of an acquired or congenital immunodeficiency disease.
  • History of Class III or IV heart failure as defined by the New York Heart Association (NYHA), unstable angina, myocardial infarction within the last 6 months, or sustained (>30 seconds) ventricular arrhythmia.
  • History of seizure disorder or other central nervous system (CNS) disease; history or current evidence of CNS involvement with MM. Note: CNS screening (e.g., lumbar puncture) is not mandatory unless symptoms are present.
  • History of other primary malignancies, except for the following:
  • Non-melanoma skin cancer (e.g., basal cell carcinoma) cured by resection.
  • Carcinoma in situ (e.g., cervical, bladder, or breast cancer) that has been cured.
  • Is pregnant, breastfeeding, or, for female subjects, is planning a pregnancy within 6 months.
  • Participation in another clinical trial within the last month.
  • Any condition which, in the opinion of the investigator, would place the subject at increased risk or interfere with the trial results.
  • Has undergone major surgery within 14 days prior to the first dose of the study drug.

• A subject will be eligible for this trial only if all of the following criteria are met:
  • Is willing and able to provide a written informed consent form before any trial-related activities are performed.
  • Must have a diagnosis of Multiple Myeloma (MM) according to the World Health Organization (WHO) 2017 revised criteria.
  • Must be diagnosed with active MM according to the International Multiple Myeloma Working Group (IMWG) criteria.
  • Must meet the definition of genetic high-risk MM as per the "2024 Chinese Expert Consensus on the Diagnosis and Treatment of High-Risk Multiple Myeloma", defined as having one or more of the following high-risk cytogenetic abnormalities (HRCA) confirmed by FISH or mitotic karyotype analysis:
  • del(17p) TP53 mutation t(4;14) t(14;16) t(14;20) 1q21 gain/amplification (defined as copy number ≥ 4) Del 1p Note: 1q21 amplification alone does not define cytogenetic high risk.
  • Must have a documented MM type that is B-cell maturation antigen (BCMA) positive and/or CD19 positive, confirmed at screening or from prior medical records.
  • Age ≥ 18 years, male or female.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at enrollment.
  • Has a life expectancy of ≥ 12 weeks.
  • Meets the following prior therapy requirements:
  • Is currently receiving or has received an induction therapy regimen containing at least a proteasome inhibitor, an immunomodulatory agent, or a monoclonal antibody as a backbone therapy.
  • Has not received more than 4 cycles of induction therapy at the time of enrollment.
  • Has had an effective response to induction therapy without evidence of disease progression per IMWG criteria.
  • Prior radiotherapy is permitted before enrollment.
  • Is scheduled to initiate maintenance and/or consolidation therapy 3 months after cell reinfusion, following successful enrollment.
  • Must have measurable disease to assess Progression-Free Survival (PFS). Measurable disease is defined by at least one of the following criteria:
  • Serum M-protein (M-spike) ≥ 0.5 g/dL.
  • 24-hour urine M-protein (M-spike) ≥ 200 mg.
  • Abnormal serum free light chain (FLC) ratio with an involved FLC level ≥ 50 mg/L.
  • For IgA MM: total serum IgA level outside the normal range.
  • Note: The presence of measurable disease is not required at enrollment; it can be determined from historical lab data. For instance, a subject who achieved a complete response after induction and has no measurable disease at enrollment is still eligible if they met any of the above criteria after their initial diagnosis.
  • Adequate organ function as defined by the following laboratory values:
  • Total serum bilirubin < 2 times the upper limit of normal (ULN).
  • Serum creatinine < ULN.
  • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) < 3 times ULN.
  • Estimated or calculated creatinine clearance (CrCl) ≥ 40 mL/min, via CKD-EPI or Cockcroft-Gault formula.
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50% of predicted value (corrected or uncorrected for anemia/alveolar volume).
  • Adequate bone marrow function defined as: Absolute neutrophil count ≥ 0.5×10⁹/L and platelet count ≥ 20×10⁹/L.
  • ECOG performance status of 0-2.
  • Left ventricular ejection fraction (LVEF) ≥ 50% with no pericardial effusion.
  • Must have recovered to ≤ Grade 1 (per CTCAE) from any Serious Adverse Event (SAE) before enrollment.
  • Able to comply with the study visit schedule and other protocol requirements.