A Single-Arm, Single-Center Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Relapsed or Refractory Multiple Myeloma
A Single-Arm, Single-Center Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Relapsed or Refractory Multiple Myeloma
This is a single arm, single center clinical study evaluating the safety and efficacy of CAR-T treatment for relapsed or refractory multiple myeloma.
This study is a single arm, single center study targeting patients with relapsed or refractory multiple myeloma (r/rMM). The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3×10^6/kg±20%~1×10^7/kg ±20% CAR positive T cells.
Inclusion Criteria:
1. Patients or their guardians understand and voluntarily sign an informed consent form and are expected to complete the follow-up examinations and treatments related to the study.
2. Aged 18-75 years, any gender.
3. Diagnosed with multiple myeloma according to IMWG diagnostic criteria.
4. Documented evidence that the patient's multiple myeloma is refractory or relapsed, defined as:
5. Measurable disease at screening based on any of the following criteria: serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours, or diagnosed with light-chain multiple myeloma in the absence of measurable disease in serum or urine: serum immunoglobulin free light chain ≥10 mg/dL and an abnormal κ/γ free light chain ratio, extramedullary measurable lesions, or presence of tumor cells in bone marrow biopsy.
6. Patients have recovered from toxicity of prior treatment, with CTCAE toxicity grade ≤2 (unless the abnormality is related to the tumor or is deemed stable by the investigator with no significant impact on safety or efficacy).
7. ECOG performance status score of 0-2 and an expected survival of more than 3 months.
8. Adequate organ function, including:
9. Establishing a required venous access for collection without any leukapheresis contraindications.
Exclusion Criteria:
1. Diagnosis or treatment of invasive malignancies other than multiple myeloma within 3 years, unless the malignancy has been curatively treated and there is no known active disease within 3 years before enrollment, or unless the patient has been fully treated for non-melanoma skin cancer with no evidence of disease.
2. Prior treatment with the following anti-cancer therapies (before leukapheresis for CAR-T cell production): received targeted therapy, epigenetic therapy, or investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter); received monoclonal antibody therapy within 21 days; received proteasome inhibitor therapy within 14 days; received immunomodulatory drug therapy within 7 days; received radiation therapy within 14 days (excluding bone marrow radiation ≤5% of bone marrow reserve).
3. Underwent hematopoietic stem cell transplantation within 2 months prior to screening.
4. History of central nervous system disorders.
5. Clinical signs of active central nervous system (CNS) involvement or manifestations of multiple myeloma meningeal involvement.
6. Diagnosed with Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or primary AL amyloidosis.
7. Positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA quantification, positive for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, cytomegalovirus (CMV) DNA, syphilis test, or Epstein-Barr virus DNA.
8. History of severe allergies (defined as Grade 2 or higher reactions) or known hypersensitivity to any active ingredients, excipients, mouse-derived products, or heterologous proteins included in this trial, including the conditioning regimen.
9. Severe cardiac diseases, including but not limited to severe arrhythmias, unstable angina, extensive myocardial infarction, New York Heart Association class III or IV heart failure, myocardial infarction within ≤6 months prior to screening, coronary artery bypass grafting (CABG) performed, except for non-vascular vagal syncope or dehydration, severe non-ischemic cardiomyopathy, and resistant hypertension.
10. Unstable systemic diseases, as judged by the investigator, including but not limited to severe liver, kidney, or metabolic diseases requiring drug treatment.
11. Had acute or chronic graft-versus-host disease (GVHD) within 6 months prior to screening or required immunosuppressive treatment for GVHD.
12. Active autoimmune or inflammatory neurological diseases (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis) and clinically significant active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome) at screening.
13. Requires emergency treatment for tumor emergencies at screening (e.g., spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome).
14. Has uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic treatment.
15. Received blood transfusions or hematopoietic cytokine drugs affecting the patient's blood counts within 2 weeks prior to screening for planned CAR-T cell production, as determined by the investigator to affect cell preparation.
16. Receiving steroids or immunosuppressive drugs within 2 weeks of screening for planned CAR-T cell production:
17. Underwent major surgery (excluding diagnostic surgery and biopsy) within 4 weeks prior to screening or has unhealed surgical wounds before enrollment.
18. Received (attenuated) live virus vaccines within 4 weeks before screening.
19. Has severe mental illness.
20. History of alcohol abuse or substance abuse.
21. Pregnant or lactating women and participants planning to become pregnant within 2 years after cell infusion or their partners planning to become pregnant within 2 years after cell infusion.
22. Patients who have contraindications to any study procedure or have other medical conditions that may place them at unacceptable risk according to the investigator 's judgment and/or clinical criteria.