Study of FasT CAR-T GC012F Injection NDMM Patients

Summary

This is a single-arm, single-center, open-label clinical study to evaluate the safety and efficacy of CAR-T in patients with NDMM.

Eligibility

Inclusion Criteria:

1. Age ≥18 when signing informed consent form（ICF）
2. Documented evidence of multiple myeloma at diagnosis as defined by IMWG guidelines ,monoclonal plasma cells in the bone marrow ≥10% and/or serum M protein ≥ 3 g/dL and/or 24h urine light chain ≥ 500 mg and/or presence of a biopsy proven plasmacytomas, not meet evidence of Smoldering Myeloma with SLiM/CRAB syptoms, and meet at least 2 of a-c or meet d of the following criteria at screening:

   1. Serum M protein ≥ 2 g/dL;
   2. Serum involved / uninvolved free light chain ratio ≥ 20;
   3. Bone marrow involved with monoclonal plasma cells ≥20% ;
   4. With Cytogenetic high-risk markers.
3. Or 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 0-3 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 ≥ 50×10\^9/L without transfusion support within 7 days before the screen;
8. Hemoglobin≥ 60 g/L;
9. Adequate functional reserve of organs:

   1. ALT/AST ≤ 2.5× ULN(Upper Limit of Normal);
   2. Creatinine clearance ≥ 15mL/min;
   3. Serum total bilirubin ≤ 1.5×ULN, except in subjects with congenital bilirubinemia,then direct bilirubin ≤ 1.5×ULN;
   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 CAR-T cell infusion, serum HCG should be negative in females with fertility both at screening and baseline;
12. Subjects must sign a written informed consent.

Exclusion Criteria:

1. Patients who are transplant eligible high-risk patients and plan to adopt auto/allo-transplantation
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. Evidence of serious mental disorders or changes in mental status, or the presence of central nervous system or diseases, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or autoimmune diseases involving CNS;
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) The use of a dedicated central venous catheter is permitted;
10. Confirmed or suspected CNS involved;
11. A positive virological result for any of the following: HIV, HCV, HBsAg（If HBcAg positive, DNA copies must below the LOQ）, TPPA;
12. Other severe viral or bacterial infections or uncontrolled systemic fungal infections are present;
13. Severe allergic history or allergic constitution;
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 physiological, family, social, and geographical factors, etc., and inability to comply with the research program and follow-up plan;
18. Pregnant or lactating women;
19. Investigator assessment deemed to be ineligible.

Conditions2

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