CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

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

1.Volunteer to participate in the clinical trial; the participants themselves fully understand and are informed of this study, and sign the informed consent form and are willing to follow and able to complete all trial procedures;

2.Age ≥ 18 years, male or female;

3.Participants must have newly diagnosed with multiple myeloma according to International Myeloma Working Group diagnostic criteria 2014 ;

4.Measurable disease based on at least one of the following parameters (International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma 2016); the values for these parameters obtained up to 60 days prior to signing the Informed Consent Form including the results at the time of diagnosis may be used.

1. Serum M-protein ≥ 1.0 g/dL;
2. Urine M-protein ≥ 200 mg/24 hr;
3. Serum free light chain (FLC): involved FLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.

   5.Known to have the following high risk factors, i.e. At least one of the following conditions is met:

   1)Meet any one or more of the cytogenetic criteria: del (17p); t (4; 14); t (14; 16); t (14; 20); 1q21 amplification ≥ 4 copies; 2)R-ISS stage 3; R2-ISS stages 3 and 4; 3)Presence of soft tissue extramedullary plasmacytoma 4)2%-5% in peripheral plasma cells;

   6.Eastern Cooperative Oncology Group (ECOG) score 0-2;

   7.Participants should meet the following test results (repeat tests are allowed):

   1)Hematology: Absolute neutrophil (ANC) count ≥ 1.0 × 109/L; Platelet (PLT) ≥ 50 × 109/L; Hemoglobin (Hb) ≥ 7.5 g/dL; 2)Blood chemistry: Endogenous creatinine clearance ≥ 40 mL/min (see Appendix 1 using the Cockcroft-Gault formula); Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin ≤ 1.5 × ULN; 3)International normalized ratio (INR), or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

   8.Venous access required for collection can be established and there is no contraindication for cell collection.

   9.Females of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be willing to use effective and reliable contraception for at least 12 months after CT071 infusion.

   10.A male participant, if sexually active with a female of childbearing potential, is willing to use a highly effective and reliable method of contraception for 1 year after receiving trial treatment. All male participants absolutely refrain from donating sperm during the trial and for 1 year after receiving trial treatment.

   Exclusion Criteria:

   Participants were not enrolled in the trial if they met any of the following criteria:
   1. Patients with non-secretory MM.
   2. Prior treatment for MM other than up to 2 cycles of (bortezomib, lenalidomide, dexamethasone) for induction, including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulators, targeted therapy, radiotherapy (patients are eligible for this trial if the radiation field covers ≤ 5% bone marrow reserve regardless of the end date of radiotherapy), epigenetic therapy, etc.
   3. Pregnant or lactating females.
   4. Patients with severe mental disorders or altered mental status, history of central nervous system disease, such as epilepsy, intracranial hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, memory impairment, spinal cord compression, psychiatric disease or any disease involving the central nervous system, or suspected central nervous system (CNS) metastasis, or any autoimmune disease involving the CNS, with or suspected CNS infiltration.
   5. Participants had other malignancies, including the following that were considered to have been successfully treated: non-metastatic basal cell or squamous cell skin cancer, non-metastatic prostate cancer, carcinoma in situ of the breast or cervix, and non-muscle invasive bladder cancer.
   6. Active autoimmune disease that results in end organ damage or requires systemic immunosuppressive/systemic disease modifying drugs, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and other patients requiring long-term immunosuppressive therapy.
   7. Have any uncontrolled active infection (defined as exhibiting persistent signs or symptoms associated with infection that do not improve despite appropriate anti-infective therapy), or other serious active viral, bacterial, or uncontrolled systemic fungal infection. I
   8. Positive test results for biomarkers of any of the following pathogenic microorganisms: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody (TPPA), hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) (core antigen \[HBcAb\] positive must have DNA copies below the lower limit of normal).
   9. Vaccination with live attenuated vaccine or mRNA vaccine within 8 weeks and inactivated vaccine within 4 weeks prior to screening.
   10. Patients who are allergic or intolerant to lymphodpletion drugs, tocilizumab, or allergic to the ingredients of CT071 cell infusion preparation (DMSO); Or previous history of other severe allergies, such as anaphylactic shock.
   11. Clinically significant cardiac abnormalities, including but not limited to:

   1)Uncontrolled congestive heart failure (New York Heart Association Class III or IV heart failure, see Appendix 3); 2)Myocardial infarction, coronary artery bypass grafting or unstable angina within 6 months prior to apheresis; 3)History of clinically significant uncontrolled cardiac arrhythmias such as ventricular arrhythmias; 4)History of severe non-ischemic cardiomyopathy; 5)Left ventricular ejection fraction (LVEF) \< 50%, diagnosed by echocardiography, without clinically significant ECG abnormalities; 6)Other heart disease that, in the opinion of the investigator, may jeopardize the health of the participant when participating in this clinical trial.

   12.Participants with known or suspected chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of the predicted normal value of spirometry, or other lung disease that, in the judgment of the investigator, significantly affects lung function or affects the safety of the participant, such as asthma, interstitial lung disease, diffuse lung disease, pulmonary infection, pulmonary embolism, etc.

   13.No need for supplemental oxygen for maintenance and oxygen saturation \< 92% in room air.

   14.Participant has a history of stroke or seizure within 6 months prior to the screening period.

   15.Has had major surgery before screening, or is planned to undergo major surgery after the trial treatment (excluding cataract and other surgery under local anesthesia). The investigator must discuss with the sponsor to determine whether a surgery is major surgery before enrolling the participant in the trial.

   16.The participant has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 from toxicities attributable to previous treatments, except for alopecia, peripheral neuropathy, and other events that, in the judgment of the investigator, are unlikely to result in lymphodepletion or cumulative toxicities of CT071 treatment; 17.Other conditions considered inappropriate for participation in this clinical trial by the investigator.

主要终点：Adverse Events (AE) after CT071 infusion · An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). · From first dose of study drug administration to end of treatment (up to 24 months)；Overall response rate (ORR) · ORR defined as proportion of patients achieving partial response or better based on International Myeloma Working Group defined response criteria · From first dose of study drug administration to end of treatment (up to 24 months)；Recommended Phase II Dose of CT071 in patients with high-risk newly diagnosed multiple myeloma · Evaluate Dose limited toxicity and adverse events after CT071 infusion · Assessed from the date of first dose of study treatment until 28 days
次要终点：Minimal residual disease (MRD) negative rate；Complete response/stringent complete response (CR/sCR) rate；Duration of response (DOR)；Progression-free survival (PFS)；Time to response (TTR)；Time to best response (TTBR) as assessed by the investigator；Overall survival (OS)；Peak Plasma Concentration (Cmax) of CAR T cells

• Chimeric antigen receptor modified T cells Infusion · EXPERIMENTAL · Chimeric antigen receptor modified T cells chimeric antigen receptor T cells

This trial is a single-arm, single-center, open-label clinical trial to evaluate the safety, efficacy, and metabolism kinetics of CT071 in patients with high-risk newly diagnosed multiple myeloma.