Impact of Low-intensity Chemotherapy Combined With Short-course Blinatumomab on Allo-HSCT in Adults With Ph- B-ALL

Официальное название

Impact of Low-Intensity Chemotherapy Combined With Short-Course Blinatumomab on Allo-HSCT in Adults With Newly Diagnosed Ph-B-ALL: A Single-Arm, Prospective, Multicenter, Phase II Study

Обзор

This single-arm, prospective, multicenter, phase II study will enroll newly diagnosed Philadelphia chromosome-negative (Ph-) acute B-cell lymphoblastic leukemia (B-ALL) patients aged 18-60 years. Participants will receive sequential low-intensity chemotherapy followed by a two-week blinatumomab induction therapy. Treatment Protocol 1. Low-intensity chemotherapy (VIP regimen) * V (Vincristine): 1.4 mg/m² (max 2 mg) on days 1 and 8. * I (Idarubicin): 8 mg/m²/day on days 1 and 8. * P (Prednisone): 60 mg/m²/day (max 100 mg/day) or equivalent dexamethasone dose on days 1-14. 2. Sequential induction therapy: * Blinatumomab administered for 2 weeks following the VIP regimen. 3. Consolidation therapy for morphological complete remission (CR) * Patients achieving CR receive two cycles of consolidation chemotherapy: * Cycle 1: VDCP regimen (Vincristine, Daunorubicin, Cyclophosphamide, Prednisone). * Cycle 2: VP + HD-MTX regimen (Vincristine, Prednisone + High-Dose Methotrexate). 4. Allogeneic hematopoietic stem cell transplantation (allo-HSCT): * Patients with multiparameter flow cytometry-confirmed minimal residual disease (MRD)-negative status proceed to allo-HSCT. Patients achieving morphological complete remission (CR) will undergo two cycles of consolidation chemotherapy. Those with minimal residual disease (MRD)-negative status confirmed by multiparameter flow cytometry (MFC) or next-generation sequencing (NGS) will proceed to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary endpoint is 18-month relapse-free survival (RFS) rate, the secondary endpoints were composite response rate (CRc: CR + CR with incomplete hematologic recovery \[CRi\]), MRD-negative rate (assessed by MFC/NGS),18-month overall survival (OS) post-transplant, non-relapse mortality (NRM), cumulative incidence of acute/chronic graft-versus-host disease (GVHD), cumulative relapse rate and 18-month GVHD-free/relapse-free survival (GRFS) post-transplant.

Вмешательства

• Препарат Blinatumomab plus Reduced-dose Chemotherapy
  Newly diagnosed Philadelphia chromosome-negative acute B-cell lymphoblastic leukemia (Ph-negative B-ALL) patients aged 18-60 years were enrolled. Treatment Protocol 1. Low-intensity chemotherapy (VIP regimen) * V (Vincristine): 1.4 mg/m² (max 2 mg) on days 1 and 8. * I (Idarubicin): 8 mg/m²/day on days 1 and 8. * P (Prednisone): 60 mg/m²/day (max 100 mg/day) or equivalent dexamethasone dose on days 1-14. 2. Sequential induction therapy: * Blinatumomab administered for 2 weeks fol

Первичные конечные точки

• RFS [Срок оценки: three year]

Критерии участия

Критерии включения

Patients (Age 18-60 years ) with an ECOG performance status of 0-2 and HCT-CI score <3.

2\. Diagnosis: Confirmed Philadelphia chromosome-negative (Ph-) acute B-cell lymphoblastic leukemia (B-ALL) by:

• Bone marrow morphology
• Cytochemistry
• Immunophenotyping (CD19-positive by flow cytometry, ≥20% positivity on leukemic cells)
• Chromosomal analysis
• Molecular/genetic testing. 3. Planned allo-HSCT candidates must have an eligible hematopoietic stem cell donor, including:
• HLA-matched sibling donors
• Unrelated donors (9/10 or 10/10 HLA allele-matched by high-resolution typing)
• Haploidentical related donors. 4. No significant organ dysfunction:
• Liver: ALT/AST ≤3× upper limit of normal (ULN); total bilirubin ≤2× ULN.
• Kidney: BUN and serum creatinine ≤1.25× ULN.
• Cardiac:
• No acute myocardial infarction or severe arrhythmia on ECG.
• Left ventricular ejection fraction (LVEF) ≥50% on echocardiography; no significant cardiomegaly, valvular disease, or congenital heart defects.
• Pulmonary: FEV1, FVC, and DLCO ≥60% of predicted values. 5. Contraception:
• Men, women of childbearing potential (postmenopausal women must be amenorrheic for ≥12 months), and their partners must use investigator-approved effective contraception during treatment and for ≥12 months after the last study intervention.

6\. Informed consent: Patients and their legal guardians must provide written informed consent, demonstrate willingness to undergo allo-HSCT, and agree to comply with treatment protocols, follow-up schedules, and laboratory tests.

Критерии исключения

• Non-de novo patients(i.e., relapsed/refractory disease).
• BCR-ABL1 fusion gene-positive (Ph+ ALL confirmed by molecular testing).
• Uncontrolled active infections or viral diseases:

• Active bacterial, viral, or fungal infections requiring treatment.
• Hepatitis B: HBsAg-positive or HBcAb-positive with detectable HBV DNA in peripheral blood.
• Hepatitis C: HCV antibody-positive with detectable HCV RNA.
• Syphilis: Positive TRUST test.
• HIV: HIV antibody-positive.
• Major organ dysfunction or comorbidities:

• Cardiovascular:
• Uncontrolled hypertension, hypertensive crisis, or encephalopathy.
• History of congestive heart failure (CHF), unstable angina, clinically significant arrhythmias (e.g., ventricular fibrillation, ventricular tachycardia).
• Arterial thrombosis within 3 months (e.g., stroke, transient ischemic attack).
• Symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) within 6 months.
• Coronary angioplasty, defibrillation, or other high-risk cardiovascular procedures.
• Pulmonary: Severe respiratory insufficiency.
• Gastrointestinal: Active bleeding within 3 months.
• Uncontrolled concurrent illnesses that may compromise safety or study integrity.
• Active or untreated central nervous system (CNS) involvement (e.g., CNS leukemia, epilepsy requiring therapy).
• Pregnancy, lactation, or plans for pregnancy within 1 year post-infusion or during the study period.
• Uncontrolled active infections (excluding uncomplicated UTIs or upper respiratory infections).
• Hypersensitivity to blinatumomab or its components.
• Inability to provide informed consent or comply with study procedures.
• Investigator discretion: Any condition deemed to jeopardize patient safety or interfere with study objectives.

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

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06930105 · SHSYXY-Blina-Ph-B ALL-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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