Refractory/relapsed acute B-cell lymphoblastic leukemia (B-ALL), or acute B-cell lymphoblastic leukemia (B-ALL) with positive minimal residual disease (MRD) despite achieving morphological complete remission (CR) via induction chemotherapy .
Conditions
Interventions
Experimental Group:According to the "3+3" dose escalation method, the three dose groups of A-319, namely 1.8, 3.6 and 5.0µg/kg, are planned to be evaluated. After 4 weeks of administration in each dos
Sponsors
Shanxi Bethune Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. For refractory/relapsed acute B-cell lymphoblastic leukemia, all of the following criteria must be met: 1) Age between 18 and 75 years old (inclusive), with no gender restrictions; 2) Diagnosed with refractory or relapsed acute B-cell lymphoblastic leukemia with positive CD19 expression. The definition of refractory or recurrent: Ineffective to conventional induction chemotherapy; Early recurrence (recurrence within 12 months of the first remission); Recurrence occurred 12 months after the first remission, and re-induction treatment with the original regimen failed. The second or more relapses, or relapse after autologous hematopoietic stem cell transplantation (Auto-HSCT), or relapse after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). (Philadelphia chromosome-positive [Ph+] patients must have received treatment with at least one tyrosine kinase inhibitor (TKIs); 3) The physical condition score of the Eastern Cancer Collaboration Group (ECOG) is less than or equal to 2 points; 4) The patient has at least 5% bone marrow blasts (morphological determination); 5) Life expectancy is at least 3 months; 6) The patient is able to sign the informed consent form and comply with the requirements of the protocol; If the patient is unable to sign the informed consent form, it must be signed by his or her legal guardian or agent. 2. For acute B-cell lymphoblastic leukemia that has achieved CR after induction chemotherapy but still has MRD positive, all of the following criteria must be met: 1) Age between 18 and 75 years old (inclusive), with no gender restrictions; 2) Diagnosed as acute B-cell lymphoblastic leukemia with positive CD19 expression; 3) B-ALL with at least two cycles of chemotherapy # induction therapy achieving complete hematological response (CR) and positive MRD. Positive MRD is defined as the detection of nucleated blasts >=10^-4. Patients with Philadelphia chromosome-positive [Ph+] must be treated with tyrosine kinase inhibitors (TKIs) in combination with chemotherapy. 4) The physical condition score of the Eastern Cancer Collaboration Group (ECOG) is less than or equal to 2 points; 5) The patient is able to sign the informed consent form and comply with the requirements of the protocol; If the patient is unable to sign the informed consent form, it must be signed by his or her legal guardian or agent.
Exclusion criteria
Exclusion criteria: 1) Central nervous system leukemia (determined by cerebrospinal fluid [CSF] analysis) or acute lymphoblastic leukemia with clinically relevant lesions of the central nervous system; 2) Burkitt's leukemia, testicular infiltration in acute lymphoblastic leukemia; 3) There was a history of malignant tumors other than ALL within 5 years before initiating the treatment specific to the regimen. However, the following situations are excluded: malignant tumors that have received curative treatment, have no known active diseases in the 5 years prior to enrollment, and the treating physician considers the risk of recurrence to be low. Fully treated non-melanoma skin cancer or malignant lentigoma with no evidence of disease recurrence. Cervical carcinoma in situ that has received adequate treatment and has no evidence of disease recurrence. Breast ductal carcinoma in situ that has received adequate treatment and has no evidence of disease recurrence. Intraepithelial neoplasia of the prostate without evidence of prostate cancer; 4) Those who have undergone allogeneic hematopoietic stem cell transplantation and are accompanied by grade 2-4 acute graft-versus-host disease (GVHD) or are in chronic graft-versus-host disease and require the use of immunosuppressants; 5) Autologous hematopoietic stem cell transplantation (Auto-HSCT) was received within 6 weeks before the start of the study drug treatment, and allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was received within 3 months. 6) Study systemic treatment of combined chemotherapy, radiotherapy or GVHD within 2 weeks before the start of drug therapy; 7) If the researcher determines that the patient has diseases, medical conditions or social factors that may affect the research results or compliance, the protocol stipulates that the following conditions cannot participate in this study: Uncontrolled acute infection or confirmed bacteremia, known human immunodeficiency virus (HIV) infection or acute phase of hepatitis B or hepatitis C Patients with severe dyspnea, pulmonary insufficiency or continuous oxygen inhalation, New York Heart Association [NYHA] grade 3 or 4 cardiac insufficiency, myocardial infarction within 6 months before administration, unstable angina pectoris, stroke or transient ischemic attack, severe arrhythmia, and uncontrolled hypertension (systolic blood pressure >180mmHg and/or diastolic blood pressure >100) "mmHg;" 8) The laboratory test regulations are as follows: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be greater than three times the upper limit of the normal value (> 3× ULN), and if accompanied by liver metastasis, they should be greater than five times the upper limit of the normal value (> 5×ULN). Total bilirubin is greater than 1.5 times the upper limit of the normal value (> 1.5×ULN); Creatinine clearance rate 1.6 (unless anticoagulation therapy is received); The dosage of oral anticoagulant therapy remains unchanged (at least 14 days), such as oral warfarin. The INR must be <=3.0 and there must be no bleeding tendency (i.e., no bleeding within 14 days before the first use of the study drug). Low-molecular-weight heparin is allowed for the subjects. 9) Previous anti-CD19 treatment (including CAR-T), or received immunotherapy (such as rituximab) within 4 weeks before A-319 treatment; 10) Accompanied by adve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Analysis; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;Efficacy Analysis;Biomarker; | — |
Countries
China
Contacts
Public ContactTian Weiwei
Shanxi Bethune Hospital
Outcome results
None listed