Overview

This is a single arm, single center clinical study evaluating the safety and efficacy of CAR-T treatment for multiple myeloma.

Eligibility

Inclusion Criteria:

1. Patients or their guardians understand and voluntarily sign the informed consent form, and are expected to complete the follow-up examination and treatment of study procedures;
2. Aged 18-75 years, male or female;
3. According to IMWG diagnostic criteria, diagnosed with multiple myeloma;
4. Patients with documented multiple myeloma disease as relapsed refractory or primary refractory, defined as: a) relapsed refractory: no response to salvage therapy (no response defined as failure to achieve minimal response [MR] or disease progression on treatment), or disease progression within 60 days of the last treatment, or disease progression in patients who have achieved MR or above remission; b) primary refractory: never achieved MR or above response to any treatment, including never achieved MR or above remission, but M protein changes are not large, patients without evidence of clinical progression and patients who have primary refractory, progressed, and met the definition of progression.
5. the presence of measurable disease at screening as determined by 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 diagnosis of light chain multiple myeloma without measurable disease in serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin κ/γ free light chain ratio; extramedullary measurable disease; the presence of tumor cells in the bone marrow as detected;
6. the patient has recovered from the toxicity of previous treatment, that is, CTCAE toxicity grade < 2 (unless the abnormality is tumor-related or judged by the investigator to be stable, it has little effect on safety or efficacy);
7. ECOG performance status score 0 to 2 and expected survival greater than 3 months;
8. Appropriate organ function:

        alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN); aspartate
        aminotransferase (AST) ≤ 3 times the ULN; total bilirubin ≤ 1.5 times the ULN; Serum
        creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 30 mL/min (calculated by
        Cockcroft-Gault formula); Intraventricular oxygen saturation ≥ 92%; Left ventricular
        ejection fraction (LVEF) ≥ 45%, no pericardial effusion confirmed by echocardiography, no
        clinically significant electrocardiographic findings; no clinically significant pleural
        effusion; 9. venous access for collection can be established, no contraindications for
        leukocyte collection.
        Exclusion Criteria:
          1. Diagnosis or treatment of another invasive malignancy other than multiple myeloma
             within 3 years, with the following exceptions: malignancy treated with curative intent
             and no known active disease ≥ 3 years prior to enrollment; or adequately treated
             non-melanoma skin cancer with no evidence of disease;
          2. previous anticancer therapy (prior to blood collection for CAR-T preparation) as
             follows: targeted therapy, epigenetic therapy, or investigational agent within 14 days
             or at least 5 half-lives (whichever is shorter), or invasive investigational medical
             devices; monoclonal antibody therapy within 21 days; proteasome inhibitor therapy
             within 14 days; immunomodulator therapy within 7 days; and radiotherapy within 14 days
             (except for bone marrow reserve with ≤ 5% field coverage);
          3. Any hematopoietic stem cell transplantation within 2 months before screening;
          4. History of central nervous system diseases;
          5. known active central nervous system (CNS) involvement or clinical signs of meningeal
             involvement in multiple myeloma;
          6. Waldenström macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
             endocrinopathy, monoclonal proteinopathy, and skin changes) or primary AL amyloidosis
             at screening;
          7. Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb)
             positive and peripheral blood HBV DNA quantitative detection positive; hepatitis C
             virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive;
             cytomegalovirus (CMV) DNA detection positive; syphilis detection positive;
             Epstein-Barr virus DNA detection positive;
          8. Patients with a history of severe allergy [a history of severe allergy is defined as a
             secondary or above allergic reaction, any of the following clinical manifestations
             occur when allergic reactions occur: airway obstruction (runny nose, cough, wheezing,
             dyspnea), tachycardia, hypotension, arrhythmia, gastrointestinal symptoms (nausea,
             vomiting), incontinence, laryngeal edema, bronchospasm, cyanosis, shock, respiratory,
             cardiac arrest] or known allergy to any of the active ingredients, excipients or
             murine products and xenogeneic proteins contained in this trial (including Qinglin
             regimen);
          9. Patients with severe heart disease, including but not limited to severe arrhythmia,
             unstable angina pectoris, massive myocardial infarction, New York Heart Association
             class III or IV cardiac insufficiency, myocardial infarction ≤ 6 months before
             screening or coronary artery bypass grafting (CABG), a history of unexplained syncope
             and non-vasovagal or dehydration caused by, a history of severe non-ischemic
             cardiomyopathy, refractory hypertension (refractory hypertension is defined as: the
             use of reasonable tolerable adequate doses of ≥ 3 antihypertensive drugs (including
             diuretics) on the basis of lifestyle improvement for > 1 month of blood pressure is
             still not up to standard or taking ≥ 4 antihypertensive drugs blood pressure can be
             effectively controlled);
         10. unstable systemic diseases judged by the investigator: including but not limited to
             severe liver, kidney or metabolic diseases requiring drug treatment;
         11. Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months before
             screening, or need to receive immunosuppressive agents for GVHD;
         12. Patients with active autoimmune or inflammatory diseases of the nervous system (e.g.,
             Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically
             significant active cerebrovascular disease (e.g., cerebral edema, posterior reversible
             encephalopathy syndrome (PRES));
         13. Neoplastic emergencies (such as spinal cord compression, intestinal obstruction,
             leukostasis, tumor lysis syndrome, etc.) requiring emergency treatment before
             screening or reinfusion;
         14. presence of uncontrollable bacterial, fungal, viral, or other infections requiring
             antibiotic therapy;
         15. Hematopoietic cytokine drugs that have been transfused or have an effect on the
             hemogram of patients such as erythropoietin (EPO), granulocyte colony-stimulating
             factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) within 2
             weeks of blood collection scheduled for CAR-T preparation at screening, and have an
             effect on cell preparation as judged by the investigator.
         16. Receiving hormonal or immunosuppressive agents at screening within 2 weeks of blood
             collection scheduled for CAR-T preparation and having an effect on cell preparation as
             judged by the investigator.
        1) Corticosteroids: subjects who are receiving systemic steroid therapy within 2 weeks of
        blood collection scheduled for CAR-T at screening and require chronic systemic steroid
        therapy during treatment as judged by the investigator (except for inhaled or topical use);
        and subjects who are receiving systemic steroid therapy within 72 hours before cell
        reinfusion (except for inhaled or topical use); 2) Immunosuppressants: subjects who are
        receiving immunosuppressive agents within 2 weeks of blood collection scheduled for CAR-T
        at screening; 17. Patients who have undergone major surgery (except diagnostic surgery and
        biopsy) within 4 weeks before Qinglin or plan to undergo major surgery during the study
        period, or whose surgical wounds have not completely healed before enrollment; 18. Patients
        who have received (attenuated) live viral vaccines within 4 weeks before screening; 19.
        patients with severe mental illness; 20. Alcoholics or those who have a history of drug
        abuse; 21. Pregnant or lactating women, and female subjects who plan to become pregnant
        within 2 years after cell reinfusion or male subjects whose partners plan to become
        pregnant within 2 years after cell reinfusion; 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.