CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

Participants must meet all of the following criteria to be enrolled:

1. Patients must voluntarily sign the informed consent form (ICF) and must be willing and be able to adhere to the trial visit schedule and other protocol requirements and agree to be in long term follow-up (LTFU) for up to 15 years as mandated by the regulatory guidelines.
2. Age ≥ 18 years;
3. Patients with R/RMM who have received at least 3 prior lines of therapy, including at least 1 proteasome inhibitor and at least 1 immunomodulator (IMiD). Patients with RRpPCL had received at least 1 prior line of therapy. Number of lines of therapy was defined according to the guidelines provided in Rajkuma\[1\]r 2015 . Patients must have received at least 1 complete cycle of therapy for each line of therapy.
4. According to multiple myeloma IMWG 2016 and plasma cell leukemia IMWG 2013, patients must have progressive disease following or during the last treatment.
5. Patients must have measurable disease based on at least one of the following parameters:
6. Expected survival \> 12 weeks;
7. Eastern Cooperative Oncology Group (ECOG) score 0- 1 ;
8. Patients should meet the following test results
9. Female patients of childbearing potential must have a negative pregnancy test at screening and prior to receiving lymphodepletion therapy and are willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment and are absolutely prohibited from donating eggs for 1 year after receiving study treatment infusion during the study ;Male patients are willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment if they are sexually active with a female of childbearing potential. Sperm donation is absolutely prohibited within 1 year following study treatment infusion for all male patients during the study.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Patient has any significant condition(s), laboratory abnormality or psychiatric illness that would impair the ability of the patient to receive or tolerate the planned treatment or in the opinion of the investigator, participation would not be in the best interest of the patient (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
3. Patients seropositive for HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection. History of treated hepatitis B or C is permitted if the viral load is undetectable per qPCR and or nucleic acid testing;
4. Patients with any uncontrolled active infection, including but not limited to patients with active tuberculosis (investigator 's judgment);
5. Toxicities caused by previous treatment have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except alopecia and other events that are judged tolerable by the investigator;
6. Previous allogeneic stem cell transplantation; autologous stem cell transplantation within 12 weeks prior to signing informed consent;
7. Have received treatment for the disease within 14 days before informed consent
8. Have received cell therapy within 28 days before informed consent.
9. Systemic glucocorticoids equivalent to \> 15 mg/day prednisone within 7 days prior to informed consent, with the exception of topical glucocorticoids;
10. Vaccination with live attenuated vaccines , inactivated vaccines or RNA vaccines within 4 weeks prior to informed consent;
11. Allergic or intolerant to lymphodepletion, tocilizumab, or allergic to components (DMSO) in CT0596 CART cell infusion preparation; or previous history of other serious allergies such as anaphylactic shock;
12. Patients Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at Screening;
13. Patients with any of the following cardiac conditions within 6 months prior to screening:
14. Patients who require supplemental oxygen to maintain oxygen saturation \> 92%; or Patients with known or suspected COPD who have Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted normal on spirometry;
15. Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis and other diseases requiring long-term immunosuppressive therapy;
16. Patients with second primary malignancies are not eligible if the second primary malignancy has required treatment within the past 2 years or is not in complete remission. Exceptions include the following that have been successfully treated - nonmetastatic basal cell or squamous cell skin carcinoma, non-metastatic prostate cancer, carcinoma-in-situ of breast or cervix, non-muscle invasive bladder cancer
17. Patients with symptomatic central nervous system (CNS) disease or suspected CNS metastases;
18. Major surgery within 2 weeks before informed consent or planned during the study period or within 4 weeks after giving study treatment (excluding local anesthesia such as cataract)

主要终点：Adverse Events (AE) after CT0596 infusion · An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria · 12 months after CT0596 infusion；MTD and/or dose range · Evaluate Dose limited toxicity and recommended dosage range after CT0596 infusion · 12 months after CT0596 infusion
次要终点：Overall response rate (ORR) as assessed by the investigator；Complete response/stringent complete response (CR/sCR) rate；Rate of very good partial response (VGPR) and above；Duration of response (DOR)；Minimal residual disease (MRD) negative rate；Time to response (TTR)；Progression-free survival (PFS)；Peak value of CART cells

• CAR-T cells Infusion · EXPERIMENTAL · chimeric antigen receptor T cells

This study is a single-arm, open-label, exploratory dose-escalation and dose-finding clinical trial to evaluate the safety, efficacy, cellular pharmacokinetics and pharmacodynamics of CT0596 cells in patients with R/R MM and PCL.RRMM and RRpPCL