A Study of Injectable BLB101 and Blincyto® in Adult Participants With R/R CD19+ B-ALL

A Randomized, Double-Blind, Positive-Controlled, Multicenter Clinical Study to Compare the Similarities in Pharmacokinetics, Efficacy, Safety and Immunogenicity Between BLB101 and Blincyto® in Adult Participants With R/R CD19+ B-ALL

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Precursor B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: BLB101 for Injection; Drug: Blinatumomab for Injection

Detailed Description

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
• Enrollment (Estimated): 212
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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: Liver and kidney function: ALT/AST ≤ 3 times the upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN; Creatinine clearance rate ≥ 60 mL/min; 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: a) At least 2 weeks after the end of cytotoxic chemotherapy drugs treatment; b) 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; c) At least 2 weeks after anti-tumor traditional Chinese medicine treatment; d) At least 3 months after CAR-T treatment; e) 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. 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. 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:

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 < 50%;
8. Participants who have received at least 28 days of targeted CD19 bispecific antibody treatment and have been ineffective (ineffectiveness is defined as the failure to achieve CR or CRh or CRi or MLFS in the efficacy evaluation);
9. Participants who have received at least 1 time of targeted CD19 CAR-T infusion and have been ineffective (ineffectiveness is defined as the failure to achieve CR or CRh or CRi or MLFS in the efficacy evaluation);
10. Participants who have received targeted CD19 bispecific antibody treatment and have achieved CR or CRh or CRi or MLFS but have relapsed within ≤ 6 months;
11. Participants who have received targeted CD19 CAR-T treatment and have achieved CR or CRh or CRi or MLFS but have relapsed within ≤ 12 months;
12. Participants who have received autologous HSCT within 6 weeks before the first administration or have received allogeneic HSCT within 3 months before the first administration;
13. Any active acute graft-versus-host disease (GvHD) grade 2-4 (according to the Glucksberg standard), or active chronic GvHD requiring systemic treatment;
14. Any systemic treatment for GVHD within 2 weeks before the first administration;
15. Participants with positive HIV antibody; participants with active HBV infection: positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA above the upper limit of normal; positive for HCV antibody and positive for HCV RNA in peripheral blood;
16. Participants have active infections (including bacterial, viral, and fungal infections) that require systemic intravenous antibiotics treatment as judged by the investigator to have clinical significance;
17. Participants with significant active cardiovascular disease within the past 6 months, including but not limited to the following conditions: ≥ III grade heart failure according to the New York Heart Association (NYHA) definition; angina pectoris, unstable angina pectoris, myocardial infarction requiring surgical treatment; uncontrolled hypertension (i.e., systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 90 mmHg) after treatment; arrhythmia not controlled; echocardiography-measured resting left ventricular function ejection fraction less than 50%; QT interval: male > 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; 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, cervical carcinoma in situ, or breast carcinoma in situ;
19. Participants with uncontrolled third space effusion (such as pleural effusion, ascites, pericardial effusion), requiring repeated drainage;
20. Participants who have had interstitial lung disease (ILD)/interstitial pneumonia in the past or currently, and deemed by the investigator not suitable for inclusion in this study;
21. Have a clear allergy to immunoglobulin or injectable belinotuzumab monoclonal antibody and its other components;
22. Within the 4 weeks prior to the administration of this study, the participant has participated in other clinical trials of intervention drugs or medical devices, or is currently receiving treatment in other clinical trials (excluding non-interventional studies);
23. Circumstances deemed unsuitable for participation in the trial by the investigator (such as, the investigator believes it may pose risks to the participant's safety or interfere with the evaluation, procedures, or completion of any other clinically significant medical history or having any other clinically significant disease at present (excluding those listed above).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BLB101 for Injection; BLB101 for injection administered via intravenous infusion at a dose of 9μg/d or 28 μg/d. One treatment cycle consists of 6 weeks, including 4 weeks of dosing followed by a 2-week treatment-free interval.Participants weighing ≥45kg received fixed dosing: In Induction Cycle 1: 9μg/d on Days1-7, followed by 28μg/d on Days 8-28, then a 14-day treatment-free period.In Induction Cycle 2: 28μg/d on Days 1-28, followed by a 14-day treatment-free period.For participants weighing <45kg, doses were calculated by body surface area (BSA): Induction Cycle 1: 5μg/m²/d (max 9μg/d) on Days1-7, 15μg/m²/d (max 28μg/d) on Days8-28, followed by a 14-day treatment-free period; Induction Cycle 2: 15μg/m²/d (max 28μg/d) on Days1-28, followed by a 14-day treatment-free period.	Drug: BLB101 for Injection; 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.
Active Comparator: Blinatumomab for Injection; Blinatumomab for injection administered via intravenous infusion at a dose of 9μg/d or 28 μg/d. One treatment cycle consists of 6 weeks, including 4 weeks of dosing followed by a 2-week treatment-free interval.Participants weighing ≥45kg received fixed dosing: In Induction Cycle 1: 9μg/d on Days1-7, followed by 28μg/d on Days 8-28, then a 14-day treatment-free period.In Induction Cycle 2: 28μg/d on Days 1-28, followed by a 14-day treatment-free period.For participants weighing <45kg, doses were calculated by body surface area (BSA): Induction Cycle 1: 5μg/m²/d (max 9μg/d) on Days1-7, 15μg/m²/d (max 28μg/d) on Days8-28, followed by a 14-day treatment-free period; Induction Cycle 2: 15μg/m²/d (max 28μg/d) on Days1-28, followed by a 14-day treatment-free period.	Drug: Blinatumomab for Injection; 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.; Other Names: Blincyto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Css	Css(Steady-State Plasma Concentration)	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)	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)	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	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	Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)
CL	CL(Clearance)	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)	Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)
fluctuation coefficient	fluctuation coefficient	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)	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)	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)	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)	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	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.	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	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.	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.	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.	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.	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).	Cycle 1, predose and Day 1, Day 8 (Cycle 1=28 days)

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): August 9, 2026
• Primary Completion (Estimated): October 10, 2027
• Study Completion (Estimated): October 10, 2028

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemic and Lymphatic Diseases; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Therapeutics; Drug Administration Routes; Drug Therapy; Injections; blinatumomab
• Other Study ID Numbers: XY2025059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to the sponsor's confidentiality policy and intellectual property restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No