JY231(JY231) Injection for the Treatment of Relapsed or Refractory B-Cell Leukemia

An Early Exploratory Clinical Study on the Safety, Tolerability, and Preliminary Efficacy of JY231 Injection in the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)

This study is an investigator-initiated single center, single arm clinical study with a target population of patients with relapsed or refractory B cell leukemia. It is an early exploratory clinical study of the safety, tolerability and initial efficacy of JY231 injection in the treatment of relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL).

This is an open-label, single-arm study to evaluate the efficacy and safety of in vivo Chimeric Antigen Receptor T-Cell(CAR-T cell) therapy in patients with relapsed refractory B-cell Acute Lymphoblastic Leukemia (B-ALL). Upon enrollment, subjects will receive an intravenous infusion of the JY231 preparation. Following the infusion, subjects will be hospitalized for one month for observation, and subjects will be evaluated for safety and efficacy. Subjects will be followed for up to 15 years to determine if the disease is under control.

Inclusion Criteria:

1. Age 18~75 years old, gender is not limited;

2. Patients with a diagnosis of Cluster of Differentiation 19 positive(CD19+) B-ALL confirmed by flow cytometry or immunohistochemistry according to the criteria of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);

3. Meet the diagnosis of relapsed/refractory (relapsed/refractory) r/r CD19+ B-ALL, including any of the following:

   A.relapse within 12 months of first remission; B.initial refractory treatment that does not achieve complete remission after two doses of standard chemotherapy, or complete remission or relapse after first-line or multiple lines of salvage therapy;

   C.Patients with Ph+-ALL (Philadelphia chromosome-positive) in whom relapse or refractory is defined as meeting any of the following:

   ① Relapse or refractory after treatment with at least two tyrosine kinase inhibitor (TKI) agents or intolerance to TKI-type agents;

   ② Resistance or failure to achieve remission after receiving second-line TKI therapy;

   ③ Not suitable for TKI therapy;

4. Bone marrow cytomorphology with >5% prolymphocytes + juvenile lymphocytes; or flow Minimal Residual Disease(MRD) >=0.01%

5. Serum total bilirubin ≤ 51 mol/L, serum alanine aminotransferase (ALT) and azelaic transaminase (AST) both ≤ 3 times the upper limit of the normal range, blood creatinine ≤ 176.8 mol/L, and platelets ≥ 20×109/L;

6. Echocardiography showed left ventricular ejection fraction (LVEF) ≥50%;

7. Subjects without active pulmonary infection and inspiratory finger pulse oxygen saturation ≥92%;

8. Subjects have not received radiotherapy, chemotherapy, monotherapy or other anti-ALL therapy within 1 week prior to screening;

9. Predicted survival of 3 months or more;

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

11. Subjects or their legal guardians volunteered to participate in this study and signed an informed consent form;

Exclusion Criteria:

1. Subjects with active central nervous system (CNS) leukemia;

2. Subjects with a history of active CNS disease such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;

3. Subjects who have been treated with another investigational drug within 30 days prior to screening or are still in the washout period;

4. Subjects who have had radiation therapy within 2 weeks prior to infusion;

5. Subjects with uncontrolled acute life-threatening bacterial, viral, or fungal infections (e.g., positive blood cultures ≤ 72 hours prior to infusion);

6. Subjects with unstable angina and/or myocardial infarction within 6 months prior to Screening;

7. Subjects with other prior or concurrent malignancies, with the following exceptions:

   ① Adequately treated basal cell, papillary thyroid, or squamous cell carcinoma (adequate wound healing is required prior to enrollment in the study);

   ② Cancer in situ of the cervix or breast that has been curatively treated and shows no signs of recurrence for at least 3 years prior to study entry;

   ③ primary malignancy that has been completely resected and in complete remission for ≥ 5 years.

8. Presence of subjects with arrhythmias not controlled by medical management;

9. Subjects with active neurologic autoimmune or inflammatory conditions (e.g. Guillain-Barre syndrome, amyotrophic lateral sclerosis);

10. Women who are pregnant or breastfeeding, and female subjects who plan to become pregnant within 2 years of their JY231 injection infusion or male subjects whose partners plan to become pregnant within 2 years of their JY231 injection infusion;

11. Subjects who, in the investigator's judgment and/or clinical criteria, have a contraindication to any of the investigational procedures or have other medical conditions that may place them at unacceptable risk.

12. Other conditions that, in the opinion of the investigator, should not be enrolled in this clinical study, such as poor compliance.