Early exploratory clinical study of the safety, tolerability and initial efficacy of JY231 injection in the treatment of relapsed or refractory B-cell lymphoma

This is a single-center, single-arm, open-treatment clinical study. In this study, approximately 10-20 adult and elderly patients with CD19-positive relapsed or refractory B-cell lymphoma will be enrolled for JY231 infusion therapy. The safety of JY231 was evaluated by observing adverse events after cell therapy. Evaluate the effectiveness of JY231 treatment compared to the results of the subjects' own previous standard treatment regimens or base data. Blood, bone marrow, and cerebrospinal fluid were collected before and 12 months after the JY231 infusion to detection.

Inclusion Criteria:

1. understand and sign the informed consent and are willing and able to comply with all test requirements;

2. Age 18-75 years old, gender is not limited;

3. Flow cytometry or malignant tumor cells were CD19 positive;

4. Meet the clinical criteria for r/r B-cell lymphoma, including: indolent lymphoma (iNHL), follicular lymphoma (FL) and marginal zone lymphoma (MZL); Invasive B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL), and T-lymphocyt-rich large B-cell lymphoma (TCRBCL);

5. There is at least one measurable lesion on imaging (Lugano 2014 criteria), that is, a lymph node lesion with a diameter greater than 15 mm on CT cross-sectional images or an extranodal lesion with a diameter greater than 10 mm, with a positive FDG-PET test.

6. Expected survival ≥12 weeks;

7. The ECOG (Eastern Tumor Collaboration Group) score at baseline was 0 ~ 1;

8. Adequate organ function (indicators involving liver and kidney function can be appropriately relaxed) :

   • ALT ≤3 xULN;
   • AST)≤3x ULN;
   • Total bilirubin ≤1.5 x ULN;
   • Serum creatinine ≤ 1.5x ULN, or creatinine clearance ≥60 mL/min;
   • Indoor oxygen saturation ≥92%;
   • Left ventricular ejection fraction (LVEF) ≥55%, echocardiography confirmed no pericardial effusion, no clinically significant ECG findings;
   • No clinically significant pleural effusion;

9. Sufficient who with adequate bone marrow reserve, defined as:

   Absolute neutrophil count (ANC) > 1.000 /mm3; Absolute lymphocyte count (ALC) ≥300 /mm3; Platelet ≥50.000 /mm3; Hemoglobin > 8.0g/dl;

10. Using the following drugs must meet the following conditions:

    • Steroids: Therapeutic doses of steroids must be discontinued 72 hours before JY231 infusion. Physiological replacement doses of steroids are permitted;
    • Immunosuppression: Any immunosuppressive drug must be stopped ≥4 weeks prior to enrollment;
    • Anti-proliferative therapy other than lympho-depleting chemotherapy within two weeks of infusion; CD20 antibody therapy must be discontinued within 4 weeks prior to infusion or 5 half-lives (whichever is older);
    • CNS disease prevention must be stopped 1 week before JY231 infusion (e.g., intrathecal methotrexate).

11. Fertile men, to ensure that sexual partners can effectively prevent contraception; Women who are fertile, use effective birth control and consent to use birth control throughout the study period.

Exclusion Criteria:

1. Subjects with active cerebrospinal fluid malignant cells or brain metastases, or subjects with active central nervous system (CNS) lymphoma;

2. Subjects with a history of active CNS disease, such as seizures, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;

3. Subjects who have received other study drugs within 30 days prior to screening;

4. Subjects who have previously received any anti-CD19 / anti-CD3 therapy or any other anti-CD19 therapy (except those with adequate bone marrow reserve and whose tumor is CD19-positive);

5. Patients who have previously been treated with any gene therapy product, including CAR-T therapy (except those with no CAR T in the body, normal T cell count and function, and CD19-positive tumors);

6. Subjects undergoing radiation therapy within 2 weeks prior to infusion;

7. Subjects with active hepatitis B (defined as hepatitis B virus DNA test value > 500 IU/mL) or hepatitis C (HCV RNA positive); Hiv-positive or treponem-positive subjects;

8. Subjects with an acute life-threatening bacterial, viral, or fungal infection that has not yet been controlled (e.g., positive blood culture ≤72 hours prior to infusion);

9. Participants with unstable angina pectoris and/or myocardial infarction in the 6 months prior to screening;

10. Subjects with prior or concurrent development of other malignancies, except in the following cases:

    • Adequately treated basal cell, thyroid papillary, squamous cell carcinomas (requiring adequate wound healing prior to enrollment);
    • Carcinoma in situ of cervical or breast cancer with curative treatment and no signs of recurrence for at least 3 years prior to the study;
    • The primary malignancy has been completely removed and in complete remission for ≥5 years.

11. Clinically significant ventricular arrhythmia;

12. Subjects received anticoagulant therapy within a week;

13. Active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis);

14. Pregnant or lactating women, and female subjects who are planning to become pregnant within 2 years after JY231 injection infusion or male subjects whose partners plan to become pregnant within 2 years after JY231 injection infusion;

15. Subjects who, in accordance with the investigator's judgment and/or clinical standards, are contraindicated with any study procedure or have other medical conditions that may place them at unacceptable risk.

16. Other conditions that the investigator believes should not be included in this clinical trial, such as poor compliance.