Study of YK012 in B-cell Acute Lymphoblastic Leukemia

Exclusion Criteria32

• Burkitt´s Leukemia according to World Health Organization (WHO) classification.
• History of antitumor therapy as follows, before the first dose of study drug:
• Targeted therapy with small molecule drug within 2 weeks or 5 half-lives, whichever is longer
• Targeted therapy with macromolecular drug or Immunomodulatory agent therapy within 3 weeks
• Radiotherapy or chemotherapy (except for intrathecal chemotherapy and dexamethasone), or treatment with Chinese traditional/patent medicine that has definite antitumor effect within 2 weeks
• Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter
• Receipt of any live attenuated vaccines or live virus vaccine within 4 weeks
• Autologous stem cell transplantation within 6 weeks
• History of organ transplant, or allogeneic stem cell transplantation within 12 weeks.
• Any active acute graft-versus-host disease (GvHD), grade 2-4 (according to Glucksberg criteria) or active chronic GvHD requiring systemic treatment.
• Other malignancy within 5 years, except localized malignancies that have been adequately treated or free of the disease for ≥ 5 years, e.g., basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-muscle invasive bladder cancer, localized prostate cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast.
• Active central nervous system (CNS) involvement or meningeal involvement with clinical signs, or other evidence of uncontrolled metastases to the CNS or meninges, judged by the investigator.
• a. History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis. b. Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI.
• History or evidence of cardiovascular disease, including:
• Acute coronary syndromes (e.g., myocardial infarction, unstable angina)
• Coronary angioplasty or stenting within 6 months prior to enrollment
• Clinically significant unstable arrhythmias (e.g., atrial fibrillation), however, atrial fibrillation has been controlled for over 30 days prior to the first dose of YK012 were allowed
• New York Heart Association (NYHA) stage III or higher congestive heart failure
• Left ventricular ejection fraction (LVEF) below lower limit of the study center, or LVEF\<50% if there is no lower limit at the study center
• The Fridericia-corrected QT interval (QTcF, mean of triplicate measurements) ≥ 470 msec (female) or ≥ 450 msec (male)
• Implantable defibrillator
• Clinically uncontrollable hypertension (i.e., SBP≥160 mm Hg and/or DBP≥100 mm Hg).
• Known allergy to monoclonal antibody drugs or exogenous immunoglobulin.
• History of CD19 targeted therapy and positive test result for immunogenicity of YK012 at screening.
• Any major organ surgery or significant trauma within 4 weeks prior to the first dose of YK012, or those requiring elective surgeries during the study, and all AEs associated with surgery or significant trauma have not recovered to Grade ≤1 or baseline graded by CTCAE v5.0 before the first dose of the YK012.
• Regular dose of systemic corticosteroids during 4 weeks prior to initiation of study drug, or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent during the trial, or any other immunosuppressive therapy within 4 weeks prior to study entry.
• Virological tests: Hepatitis B virus surface antigen (HBsAg) positive and/or hepatitis B core antibody (HBcAb) positive, and hepatitis B virus (HBV) deoxyribonucleic acid (DNA)\>ULN of the testing agency; Hepatitis C antibody (HCV-Ab) positive and hepatitis C virus-RNA (HCV-RNA)\>ULN of the testing agency; Anti-human immunodeficiency virus (Anti-HIV) positive. Participants will be excluded from the study if any of the above criteria is met.
• Uncontrolled active infections requiring oral or intravenous systemic therapy, except for local treatment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently).
• Pregnant or lactating women.
• Known mental disorder that may affect study compliance or poor compliance.
• Other serious systemic diseases or laboratory abnormalities or other reasons that the investigator believes are not appropriate for participating in the study.