CD19-positive precursor B-cell acute lymphoblastic leukemia in adults and children
Conditions
Interventions
Experimental group:BLB101 for Injection,Administration route: Intravenous infusion
Dose: 9 µg/day or 28 µg/day
Drug administration schedule: Each 6-week period constitutes a treatment cycle. During each cycle, the drug is administered for 4 weeks and then the drug is withheld for 2 weeks. Each participant is r
Control group:Blinatumomab for Injection (Blincyto),Administration route: Intravenous infusion
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, The First Affiliated Hospital,Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Participants must meet all of the following inclusion criteria to be included in this study: 1. Before the trial began, the trial details were known, and the participant understood and voluntarily signed the Informed Consent Form (ICF); 2. Age = 18 years old; 3. Confirmed as Philadelphia chromosome (Ph) negative and CD19 positive relapsed/refractory B-ALL (must meet: (1) Through morphological and local flow cytometry immunophenotype assessment, there are expressed CD19 primitive immature cells in peripheral blood or bone marrow, confirming the current state of relapse, and there are relevant medical records to support; (2) The proportion of primitive cells in the bone marrow is greater than 5% (measured by morphology); (3) Chromosome karyotype analysis or FISH analysis or PCR or NGS confirms Ph-negative), the Ph status needs to be reconfirmed before enrollment; 4. ECOG = 2 points; 5. The number of previous treatment lines is 1 to 2, and it meets the definition of relapse or refractory (any of the following conditions can be included in the group: (1) Late relapse: Reversal after achieving remission with previous treatment and duration = 12 months; (2) Early relapse: Remission achieved with previous treatment and duration < 12 months; (3)Refractory: Failure to achieve remission during the first induction or salvage treatment; (4) Recurrence after transplantation: Recurrence at any time after hematopoietic stem cell transplantation); 6. Weight = 45 kg; 7. Expected survival period = 3 months; 8. Organ function requirements: (1)Liver and kidney function: ALT/AST = 3 times the upper limit of normal (ULN), total bilirubin = 1.5 × ULN; (2)Creatinine clearance rate = 60 mL/min; (3)Cardiac function: Left ventricular ejection fraction (LVEF) = 50%, no severe arrhythmia; 9. Participants need to have recovered to = Grade 1 toxicity from previous treatments (according to CTCAE V6.0 standards), excluding hematological toxicity; 10. Participants need to meet the washout period from the first administration of anti-tumor treatment: (1)At least 2 weeks after the end of cytotoxic chemotherapy drugs treatment; (2)At least 5 half-lives after non-cytotoxic drugs (if the duration of 5 half-lives exceeds 4 weeks, the washout period is still counted as 4 weeks), for drugs with an unclear half-life, it is counted as more than 4 weeks; (3)At least 2 weeks after anti-tumor traditional Chinese medicine treatment; (4)At least 3 months after CAR-T treatment; (5)At least 5 half-lives after antibody drugs and antibody conjugate drugs (ADC); (if the duration of 5 half-lives exceeds 3 months, the washout period is still counted as 3 months); 11. According to the investigator's judgment, the participant's compliance can reach understanding and following the plan for visits, treatment, laboratory tests, and other research procedures, and is expected to receive the study drug for = 1 cycle; 12. (1)For female participants with reproductive capacity: Agree to take effective contraceptive measures from the start of signing the informed consent form until 6 months after the last administration of the trial drug, and agree not to donate eggs. (2)For male participants: Agree to take effective contraceptive measures from the start of signing the informed consent form until 6 months after the last administration of the trial drug, and agree not to donate sperm.
Exclusion criteria
Exclusion criteria: Participants who meet any of the following criteria are not eligible to be included in this study: 1. Participants with negative CD19 in ALL; 2. Participants with Ph-positive ALL or mixed phenotype; 3. Pregnant or lactating women; 4. Active central nervous system (CNS) leukemia (cerebrospinal fluid white blood cells = 5/µL and leukemia cells are observed); those with a history of CNS disease who have received effective treatment and achieved remission are excluded; 5. Participants with Burkitt lymphoma/leukemia; 6. Participants with isolated extramedullary disease recurrence and active ALL in the testicles; 7. Participants who have received targeted CD19 anti-tumor therapy before and have a proportion of CD19-positive leukemia cells 450 msec, female > 470 msec (according to the QTcF formula), or receiving known drugs that prolong QT/QTc interval, or having other factors that may prolong QTc interval; (7)or for those whose QT interval remains > 450 msec after treatment for QT interval prolongation; 18. Participants with a history of other malignancies within the past 5 years, but excluding cured cutaneous basal cell carcinoma, localized skin squamous cell carcinoma, cer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Steady-State Concentration(Css);AUC0-24 on Day 1(AUC0-24,d1);Composite Complete Remission Rate (CR/CRh); | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety;Immunogenicity;Other pharmacokinetic (PK) characteristics;Other efficacy indicators: complete remission rate (CRR), CR with partial hematologic recovery (CRh) rate, CR with incomplete hematologic recovery (CRi) rate, morphologic leukemia-free state (MLFS) remission;Pharmacodynamic (PD) characteristics; | — |
Countries
China
Contacts
Public ContactWang Jianxiang, Jin Jie
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, The First Affiliated Hospital,Zhejiang University School of Medicine
Outcome results
None listed