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

Официальное название

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

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат 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 resear
• Препарат 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 fulfille

Первичные конечные точки

• Css [Срок оценки: Cycle 1(Cycle 1=28 days), Day 8, Day 14, Day 21, Day 28, Day 29]
• AUC0-24,d1 [Срок оценки: Cycle 1(Cycle 1=28 days), predose and up to 24 hourspost-dose]
• CR/CRh [Срок оценки: 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)]

Вторичные конечные точки (12)

• Incidence of Adverse Events [Срок оценки: Up to 35 days after last dose / prior to subsequent anti-tumor therapy / prior to HSCT, whichever occurs first]
• Immunogenicity [Срок оценки: 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 [Срок оценки: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)]
• CL [Срок оценки: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)]
• Vz [Срок оценки: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)]
• fluctuation coefficient [Срок оценки: Cycle 1, predose and Day 1, Day 8, Day 14, Day 21, Day 28, Day 29(Cycle 1=28 days)]
• CRR [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Критерии участия

Критерии включения

Participants must meet all of the following inclusion criteria to be included in this study:

• Before the trial began, the trial details were known, and the participant understood and voluntarily signed the Informed Consent Form (ICF);
• Age ≥ 18 years old;
• 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;
• ECOG ≤ 2 points;
• 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);
• Weight ≥ 45 kg;
• Expected survival period ≥ 3 months;
• 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;
• Participants need to have recovered to ≤ Grade 1 toxicity from previous treatments (according to CTCAE V6.0 standards), excluding hematological toxicity;
• 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);
• 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;
• 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. -

Критерии исключения

Participants who meet any of the following criteria are not eligible to be included in this study:

• Participants with negative CD19 in ALL;
• Participants with Ph-positive ALL or mixed phenotype;
• Pregnant or lactating women;
• 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;
• Participants with Burkitt lymphoma/leukemia;
• Participants with isolated extramedullary disease recurrence and active ALL in the testicles;
• Participants who have received targeted CD19 anti-tumor therapy before and have a proportion of CD19-positive leukemia cells < 50%;
• 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);
• 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);
• 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;
• 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;
• 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;
• Any active acute graft-versus-host disease (GvHD) grade 2-4 (according to the Glucksberg standard), or active chronic GvHD requiring systemic treatment;
• Any systemic treatment for GVHD within 2 weeks before the first administration;
• 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;
• 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;
• 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;
• 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;
• Participants with uncontrolled third space effusion (such as pleural effusion, ascites, pericardial effusion), requiring repeated drainage;
• 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;
• Have a clear allergy to immunoglobulin or injectable belinotuzumab monoclonal antibody and its other components;
• 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);
• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07723911 · XY2025059

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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