A Randomized, Double-Blind, Positive-Controlled, Multicenter Clinical Study to Compare the Similarities in Pharmacokinetics, Efficacy, Safety and Immunogenicity Between Injectable BLB101 and Blincyto® in Adult Participants with R/R CD19+ B-ALL. Provide evidence for the approval and marketing of the drug for its targeted indication. Primary Objectives: 1. To compare the pharmacokinetic similarity between Injectable BLB101 and Blincyto® in participants with R/R B-ALL. 2. To compare the efficacy similarity between Injectable BLB101 and Blincyto® in participants with R/R B-ALL. Primary Endpoints: 1. Css and area AUC0-24,d1 of Injectable BLB101 versus Blincyto® in participants with R/R B-ALL. 2. CR/CRh within the first two induction cycles of treatment with Injectable BLB101 and Blincyto® in participants with R/R B-ALL, as assessed by the IRC per the response criteria for ALL. This study plans to enroll approximately 212 participants, who will be randomized at a 1:1 ratio into the following two groups: Test group: BLB101 for injection Control group: Blinatumomab for injection (Blincyto®) A stratified block randomization method will be adopted. The randomization stratification factors are as follows:a) Creatinine clearance (≤90 mL/min vs \>90 mL/min);b) Baseline leukemic cell proportion (≤50% vs \>50%);c) Relapsed/refractory status (first relapse vs ≥2 relapses or refractory disease). For each participant, the overall study procedure is outlined as follows: Participants will receive treatment with either BLB101 for injection or Blincyto®. Each treatment cycle consists of 6 weeks, including 4 weeks of dosing followed by a 2-week treatment-free interval. Each participant is required to complete the first 2 induction treatment cycles (i.e., an induction treatment period of up to 12 weeks), after which the participant will be considered to have fulfilled the primary study objectives.
A Randomized, Double-Blind, Positive-Controlled, Multicenter Clinical Study to Compare the Similarities in Pharmacokinetics, Efficacy, Safety and Immunogenicity Between Injectable BLB101 and Blincyto® in Adult Participants with R/R CD19+ B-ALL. Provide evidence for the approval and marketing of the drug for its targeted indication. Primary Objectives: 1. To compare the pharmacokinetic similarity between Injectable BLB101 and Blincyto® in participants with R/R B-ALL. 2. To compare the efficacy similarity between Injectable BLB101 and Blincyto® in participants with R/R B-ALL. Primary Endpoints: 1. Css and area AUC0-24,d1 of Injectable BLB101 versus Blincyto® in participants with R/R B-ALL. 2. CR/CRh within the first two induction cycles of treatment with Injectable BLB101 and Blincyto® in participants with R/R B-ALL, as assessed by the IRC per the response criteria for ALL
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
212
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 required to complete the first 2 treatment cycles. After completing the first 2 induction treatment cycles (i.e., a maximum of 12 weeks of treatment), they will be considered to have fulfilled the main research objective of this study. After 2 cycles of induction treatment, the decision will be made by the investigators based on the specific clinical circumstances.
Blinatumomab for Injection (Blincyto),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 required to complete the first 2 treatment cycles. After completing the first 2 induction treatment cycles (i.e., a maximum of 12 weeks of treatment), they will be considered to have fulfilled the main research objective of this study. After 2 cycles of induction treatment, the decision will be made by the investigators based on the specific clinical circumstances.
Css
Css(Steady-State Plasma Concentration)
Time frame: Cycle 1(Cycle 1=28 days), Day 8, Day 14, Day 21, Day 28, Day 29
AUC0-24,d1
Area under the plasma concentration-time curve from 0 to 24 hours on Day 1 (AUC0-24,d1)
Time frame: Cycle 1(Cycle 1=28 days), predose and up to 24 hourspost-dose
CR/CRh
Proportion of patients with Complete remission (CR) or complete remission with partial hematologic recovery(CRh)
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days)
Incidence of Adverse Events
Frequency, severity, and type of adverse events graded according to National CancerInstitute Common Terminology Criteria for Adverse Events (NCI CTCAE)Version (v) 6.0
Time frame: Up to 35 days after last dose / prior to subsequent anti-tumor therapy / prior to HSCT, whichever occurs first
Immunogenicity
ADA(anti-drug antibody) and Nab(neutralizing antibody)
Time frame: Cycle 1, predose and Day 29(Cycle 1=28 days); Cycle 2, Day 29(Cycle 2=28 days); or at the time of early participant withdrawal
T1/2
Plasma half-life
Time frame: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)
CL
CL(Clearance)
Time frame: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)
Vz
Vz(Terminal Apparent Volume of Distribution)
Time frame: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)
fluctuation coefficient
fluctuation coefficient
Time frame: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)
CRR
CRR is defined as proportion of participants who achieve CR(Complete remission)
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
CRh
Proportion of participants who achieve CRh(Complete Remission with Partial Hematological Recovery)
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
CRi
Proportion of participants who achieve CRi(Complete Remission with Incomplete Hematological Recovery)
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
MLFS
Proportion of participants who achieve MLFS (Morphologic Leukemia-Free State)
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
ORR
Overall response rate(ORR) is defined as the percentage of patients achieving complete remission (CR) or complete remission with
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
DOR
Duration of remission(DOR) is time from first confirmed CR, CRi, CRh, MLFS or PR to first disease relapse or death from any cause, calculated separately by each best response category. For participants converting from initial CRi/CRh to subsequent CR, DOR start date remains the date of initial CRi/CRh.
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
Minimal Residual Disease(MRD) Negativity Rate
Proportion of patients achieving MRD negativity
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
EFS
Event-Free Survival (EFS) is defined as the time interval from the date of first study drug administration to the earliest occurrence of any of the following events: treatment failure, disease relapse, or death from any cause. Treatment failure is defined as failure to achieve CR, CRh, CRi, or MLFS after treatment. Notably, participants with EFS event attributed to treatment failure will be assigned an EFS duration of 1 day.
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
OS
Overall Survival (OS)) is defined as the duration of time from treatment initiation until the participant's death due to any reason.
Time frame: End of Cycle 1 and up to (+7) days (Cycle 1=28 days); End of Cycle 2 and up to (+7) days (Cycle 2=28 days); Completion of long-term follow-up period.
Proportion of lymphocyte subsets
Flow cytometry was used to determine the proportions of T cells (CD3+/CD4+/CD8+) and B cells (CD19+) to assess immune reconstitution status.
Time frame: Cycle 1, predose and Day 1, Day 8 (Cycle 1=28 days)
Serum concentration of IgG
Serum IgG was quantitatively tested to assess B cell functional recovery.
Time frame: Cycle 1, predose and Day 1, Day 8 (Cycle 1=28 days)
Plasma concentration of cytokines
Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ).
Time frame: Cycle 1, predose and Day 1, Day 8 (Cycle 1=28 days)
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