A Study of CT0596 in Plasma Cell Leukemia

A Clinical Study to Explore the Safety, Efficacy, and Pharmacokinetics of CT0596 CAR-T Cell Injection in Patients With Plasma Cell Leukemia

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

This study is a single-arm, open-label, exploratory dose-escalation and dosefinding clinical trial to evaluate the safety, efficacy, cellular pharmacokinetics and pharmacodynamics of CT0596 cells in patients with PCL. During the trial, dose increases or decreases or dose expansion may be performed using i3+3 principle based on the safety and ,tolerability and PK data of the patients.

Inclusion Criteria:

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. PCL after inductive treatment or R/R pPCL.
4. Patients must have measurable disease。
5. Expected survival > 12 weeks;
6. Eastern Cooperative Oncology Group (ECOG) score 0- 1 ;
7. Patients should have good organ function。
8. 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. 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;
3. Patients with any uncontrolled active infection, including but not limited to patients with active tuberculosis (investigator 's judgment);
4. 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;
5. 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
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 or five half-lives before preconditioning
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. 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);
12. 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;
13. Patients with secondary plasma cell leukemia, Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at screening;
14. Patients with any of the following cardiac conditions within 6 months prior to screening:
15. 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;
16. Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis and other diseases requiring long-term immunosuppressive therapy;
17. Patients with second primary malignancies in addition to MM 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
18. Patients with symptomatic central nervous system (CNS) disease or suspected CNS metastases;
19. The patient is unable or unwilling to comply with protocol, or there are other reasons for being unsuitable to participate in this clinical study evaluated by investigators.