Clinical Study on the Safety and Efficacy of BiTE-EV in Relapsed/Refractory Acute B-Cell Leukemia

Inclusion criteria

Patients can be enrolled in the group only if they meet all of the following conditions:

• Patients with acute B lymphocytic leukemia who are clinically diagnosed as relapsed (relapsed after CAR-T treatment or relapsed after transplantation), refractory, or whose T cells cannot be used for the production of CAR-T cells.
• Tumor cells show positive expression of CD19 detected by flow cytometry or immunohistochemistry.
• The age is between 18 and 70 years old (inclusive).
• The expected survival period from the date of signing the informed consent form is greater than 3 months.
• The Eastern Cooperative Oncology Group (ECOG) performance status score is ≤ 2.
• The functions of vital organs should meet the following requirements:

• The ejection fraction (EF) is > 50%, and there is no significant abnormality in the electrocardiogram.
• The peripheral oxygen saturation (SpO2) is ≥ 92%.
• The serum creatinine (Cr) is ≤ 1.5 times the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤ 5 times the upper limit of normal (ULN), and total bilirubin (TBil) is ≤ 3 times the upper limit of normal (ULN).
• Subjects with pregnancy plans must agree to take contraceptive measures before enrolling in the study and six months after the study. If the subject is pregnant or suspected to be pregnant, they should immediately notify the investigator.
• The subject or the guardian understands and signs the informed consent form.

Exclusion criteria

If any one of the following conditions is met, the subject cannot be enrolled in the group:

• Complicated with other diseases that are not effectively controlled, including but not limited to persistent or poorly controlled infections, symptomatic congestive heart failure, unstable angina pectoris, arrhythmia, poorly controlled pulmonary diseases or mental disorders.
• Having other active malignant tumors.
• Complicated with severe infections that cannot be effectively controlled.
• Those who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), and those with peripheral blood hepatitis B virus (HBV) DNA higher than the detection limit need to be excluded; those who are positive for hepatitis C virus (HCV) antibody and positive for peripheral blood HCV RNA need to be excluded; those with positive cytomegalovirus (CMV) DNA detection; those with positive peripheral blood Epstein-Barr virus (EBV) DNA detection.
• Those who are positive for human immunodeficiency virus (HIV) antibody test or positive for syphilis test.
• Having a history of severe allergy to biological products (including antibiotics).

Patients with relapsed after allogeneic hematopoietic stem cell transplantation who have experienced grade 3 - 4 acute graft-versus-host disease (GvHD).

• Female subjects who are pregnant or in the lactation period.
• Active autoimmune diseases that require systemic immunosuppressive treatment.
• Situations that the investigator believes may increase the risk of the subject or interfere with the test results.