Study of FasT CAR-T GC012F Injection in High Risk TE NDMM Patients

This is an interventional treatment trial for Multiple Myeloma Read More

Inclusion Criteria:

• Patients should meet all of the following criteria:

  1. ≥18 years of age at the time of signing informed consent-upper age limit 70;

  2. High-risk defined as meet one or more of the following criteria at screen:

     1. R-ISS stage II or III;
     2. LDH > the upper limit of normal;
     3. Meet one or more of cytogenetic high risk defined by: del 17p, t(4:14), t(14:16); Gain 1q21≥ 4 copies;
     4. Patients with extramedullary disease;
     5. IgD or IgE subtype;
     6. Meet one or more high-risk definition of mSMART3.0;

  3. Documented evidence of multiple myeloma at diagnosis as defined by IMWG guidelines CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities)/SLiM criteria, monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytomas, and measurable secretory disease according to IMWG criteria meet one or more of the following criteria at screening:

     1. Serum M protein ≥ 1 g/dL;
     2. Urine M protein ≥ 200 mg/24h;
     3. Serum free light chain sFLC ≥ 10 mg/dL with abnormal serum immunoglobulin κ/λ free light chain ratio.
  4. ECOG score was 0-2 at screen;
  5. Estimated life expectancy ≥3 months;
  6. Absolute neutrophil count (ANC) ≥ 1.5×10^9/L without use of growth factors;
  7. Platelet count ≥ 75×10^9/L without transfusion support within 7 days before the screen;
  8. Hemoglobin≥ 80 g/L;

  9. Adequate functional reserve of organs:

     1. ALT/AST ≤ 2.5× UNL (upper normal limit);
     2. Creatinine clearance ≥ 40mL/min, or serum creatinine level ≤177μmol/L，may be calculated or measured according to local practice;
     3. Serum total bilirubin ≤ 1.5× UNL, except in subjects with congenital bilirubinemia, such as Gilbert syndrome, then direct bilirubin ≤ 1.5× UNL;
     4. The left ventricular ejection fraction (LVEF)≥50%, and no clinically significant ecg abnormalities were found;
     5. Basic oxygen saturation in natural indoor air: SPO2>92%.
  10. Adequate venous access for apheresis collection, and no other contraindications to apheresis;
  11. Subjects and sexual partner with fertility are willing to use effective and reliable method of contraception for at least 1 year after CART cell infusion, serum HCG should be negative in females with fertility both at screening andbaseline;
  12. Subjects must sign a written informed consent.

Exclusion Criteria:

• Patients should be excluded if they meet any one of the following criteria:

  1. Patients with purely non-secretory MM;
  2. Subject has had radiation therapy within 14 days of screening;
  3. Subjects has plasma cell leukemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes);
  4. Subjects has a diagnosis of primary amyloidosis, Waldenstroem's disease, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma;
  5. Having other tumors (excluding non-melanoma skin cancer and cervical cancer in situ bladder cancer and breast cancer that have been disease-free for more than 5 years);
  6. Overt clinical evidence of dementia or altered mental status; any history of central nervous system (CNS) disease or neurodegenerative disorder, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain damage, dementia, Parkinson's disease, psychosis;
  7. History of hereditary diseases such as Fanconi anemia, Schrader syndrome, Costerman syndrome, or any other known bone marrow failure syndrome;
  8. Clinically significant cardiac disease including: uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities, grade III-IV heart failure or myocardial infarction cardiac angioplasty or stenting unstable angina or other clinically significant cardiac conditions within one year prior to enrollment;
  9. Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy catheter indwelling catheter bile drainage tube or pleural/peritoneal/pericardial catheter) permits the use of a dedicated central venous catheter;
  10. Subjects is exhibiting clinical signs of meningeal involvement of multiple myeloma;
  11. A positive virological result for any of the following: HIV, HCV, HBsAg, TPPA;
  12. Other severe viral or bacterial infections or uncontrolled systemic fungal infections are present;
  13. Subjects with a history of severe hypersensitivity;
  14. There is a history of an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has resulted in terminal organ damage or requires systemic immunosuppressive/disease modulating drugs in the past 2 years;
  15. Presence of lung disease (such as pulmonary fibrosis);
  16. Subjects has had major surgery within 2 weeks before screen or has not fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study;
  17. Poor compliance due to factors such as physiological family, social geography, etc., and inability to comply with the research program and follow-up plan;
  18. Pregnant or lactating women, or men who are planned to have babies during the period of participation in the study or within 1 year of receiving treatment;
  19. Investigator assessment deemed to be ineligible.