Effectiveness and Safety of Blinatumomab and Donor Lymphocyte Infusion in Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for High-risk Ph Negative B Cell Acute Lymphoblastic Leukemia

Официальное название

Effectiveness and Safety of Blinatumomab and Donor Lymphocyte Infusion in Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for High-risk Ph Negative B Cell Acute Lymphoblastic Leukemia：Phrase II, Exploratory Study

Обзор

A single-arm trial to evaluate the effectiveness and safety of Blinatumomab and Donor Lymphocyte Infusion in maintenance therapy after allogeneic hematopoietic stem cell transplantation for high-risk Ph negative B cell acute lymphoblastic leukemia

Подробное описание

Currently, the treatment for Philadelphia chromosome (Ph)-negative adult B-cell acute lymphoblastic leukemia (B-ALL) primarily relies on traditional multi-agent combination chemotherapy. Clinical efficacy is closely associated with patient age, genetic characteristics, chemotherapy sensitivity, and minimal residual disease (MRD) status post-remission. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most critical curative approach for Ph-negative B-ALL. However, high-risk patients, such as those with refractory/relapsed B-ALL or MRD positivity before transplantation, exhibit significantly higher post-transplant relapse rates, reported at approximately 48%-59%, with a disease-free survival rate of less than 40%.

Multiple studies have reported that blinatumomab achieves complete remission rates of 33-50% in refractory/relapsed Ph-negative B-ALL. Previous research has shown that post-transplant blinatumomab is well-tolerated, with no treatment-related mortality, and the most common severe adverse event being cytopenia. The efficacy of blinatumomab as post-transplant prophylactic therapy depends on T-cell function.

Donor lymphocyte infusion (DLI) is widely used for the prevention and treatment of relapse after allo-HSCT. The investigators prior matched case-control study demonstrated that prophylactic DLI could reduce relapse and improve survival in high-risk acute leukemia patients after haploidentical peripheral blood stem cell transplantation. DLI products are rich in T lymphocytes, which can reverse T-cell exhaustion by altering the composition of cellular subsets in the patient's body, thereby exerting an anti-leukemic effect.

Based on the above rationale, the investigators are conducting this clinical study: a single-arm, phase II, multicenter trial to evaluate the efficacy and safety of blinatumomab combined with donor lymphocyte infusion as maintenance therapy in high-risk Ph-negative B-ALL patients after allo-HSCT.

Вмешательства

• Препарат BITE and DLI
  Blinatumomab dosage: Cycle 1 (starting at day 60 post-transplant):Days 1-3: 9 μg/day，Days 4-14: 28 μg/day Cycles 2-4:Days 1-14: 28 μg/day Administration method: Continuous 24-hour intravenous infusion, one cycle every 3 months. DLI eligibility criteria:No history of grade III-IV acute GVHD (aGVHD).No active aGVHD or chronic GVHD (cGVHD) at the time of infusion DLI dosage:Administered at day 120 post-HSCT, CD3+ cell dose: 1 × 10⁷/kg

Первичные конечные точки

• The 2-year leukemia-free survival (LFS) after allo-HSCT. [Срок оценки: 2 years]

Вторичные конечные точки (3)

• The 2-year overall survival（OS） [Срок оценки: 2 years]
• The 2-year cumulative incidence of relapse [Срок оценки: 2-years]
• The 2-year cumulative incidence of non-relapse mortality(NRM) [Срок оценки: 2-years]

Критерии участия

Критерии включения

• Age 14-65 years (inclusive), regardless of gender.
• Newly diagnosed B-ALL with CD19 expression on leukemic cells (regardless of CD19 positivity rate).
• Ph-negative B-ALL with high-risk features post-allo-HSCT .
• ≥2 months post-transplant with hematopoietic reconstitution.
• Bone marrow morphology in remission and MRD-negative before enrollment.
• ECOG performance status <3 and Karnofsky score ≥70.
• No history of grade III/IV graft-versus-host disease (GVHD) and no active GVHD at enrollment.
• Adequate organ function:AST and ALT ≤3× upper limit of normal (ULN), total bilirubin ≤2×ULN.Serum creatinine ≤2×ULN or creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula).Left ventricular ejection fraction (LVEF) ≥50% by echocardiography (ECHO).
• Expected survival >3 months.
• Voluntary provision of written informed consent, with ability to understand and comply with study requirements.

Критерии исключения

• History of hypersensitivity or severe adverse reactions to the study drug or structurally similar compounds, as assessed by the investigator to preclude participation.
• Pregnant or lactating women, or women of childbearing potential unwilling to use effective contraception.
• Severe cardiac dysfunction, including:Left ventricular ejection fraction (EF) <60%.Clinically significant arrhythmias (e.g., ventricular tachycardia, atrial fibrillation, second-degree heart block).Prolonged QTc interval (men >450 ms; women >470 ms).Myocardial infarction within the past year.Symptomatic coronary artery disease requiring medication.
• Severe pulmonary dysfunction (obstructive and/or restrictive ventilatory impairment).
• Severe hepatic impairment:ALT or total bilirubin (TBIL) >3× upper limit of normal (ULN).
• Severe renal impairment:Serum creatinine (Cr) >2× ULN.24-hour creatinine clearance (Ccr) <50 mL/min.
• Active infection or uncontrolled bleeding, as assessed by the investigator to preclude safe administration of the study drug.
• History of thrombosis, embolism, cerebral hemorrhage, or other significant vascular events within the past year.
• Psychiatric disorders or other conditions that impair the ability to provide informed consent or comply with study procedures.
• Major organ surgery within the past six weeks.
• Drug abuse or chronic alcoholism that may interfere with study assessments.
• Prior organ transplantation (excluding hematopoietic stem cell transplantation).
• Other conditions deemed by the investigator to make the patient unsuitable for participation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• First Affiliated Hospital of Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT07105579 · ZJU-HSCT-BITEDLI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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