Blinatumomab Combined With Venetoclax as Maintenance Therapy After Allo-HSCT in High-risk Ph Negative Acute B-cell Lymphoblastic Leukemia：a Prospective，Single-arm Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- the 2-year progression-free survival (PFS) rate post-transplantation
研究概览
简要总结
This study is a single-center, single-arm, prospective clinical trial evaluating the efficacy and safety of blinatumomab combined with venetoclax as maintenance therapy for high-risk Philadelphia chromosome-negative acute B-cell lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation .
详细描述
This study focuses on high-risk Philadelphia chromosome-negative (Ph-) acute B-cell lymphoblastic leukemia (B-ALL) patients. The primary objective is to evaluate the efficacy of blinatumomab combined with venetoclax as maintenance therapy following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients, while the secondary objective is to assess its safety. The primary endpoint is the 2-year progression-free survival (PFS) rate post-transplantation. Secondary endpoints include the 2-year cumulative relapse rate, 2-year overall survival (OS), incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative incidence of chronic GVHD, graft-versus-host disease-free and relapse-free survival (GRFS), non-relapse mortality (NRM), and the incidence of treatment-emergent adverse events (TEAEs) (defined as occurring from the start of maintenance therapy to 3 months after completion). Safety assessments include the incidence of adverse events and serious adverse events during treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Demographics : Patients aged 14-65 years, regardless of gender or race.
- •Diagnosis : Confirmed Ph-negative acute B-cell lymphoblastic leukemia (Ph- B-ALL) through bone marrow cytomorphology, cytochemistry, immunophenotyping, chromosomal analysis, and genetic mutation testing, with CD19 surface antigen expression.
- •Risk Stratification :
- •High-risk B-ALL (per NCCN 2024.V2 guidelines) or Standard-risk B-ALL with no pre-transplant remission or Standard-risk B-ALL in first complete remission (CR1) with measurable residual disease (MRD) positivity or Standard-risk B-ALL with ≥CR2 or B-ALL patients receiving reduced-intensity or non-myeloablative conditioning.
- •Transplant Eligibility : Scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a suitable donor meeting: HLA-identical sibling donor or Unrelated donor (HLA 9-10/10 high-resolution matched) or Haploidentical related donor.
- •HCT-CI Score : ≤2 (Hematopoietic Cell Transplantation-Specific Comorbidity Index).
- •ECOG Performance Status : ≤
- •Organ Function :
- •Serum creatinine ≤1.5×ULN Cardiac ejection fraction ≥50% Baseline SpO₂ >92% Total bilirubin ≤1.5×ULN; ALT/AST ≤2.0×ULN Pulmonary DLCO (hemoglobin-adjusted) ≥40% and FEV1 ≥50%
- •Post-Transplant Recovery :
- •Full donor chimerism Platelet count >50×10⁹/L Absolute neutrophil count >1.0×10⁹/L Hemoglobin >80g/L - Informed Consent : Patient and legal guardian must provide written informed consent, comply with treatment protocols, follow-up visits, and laboratory assessments.
排除标准
- •Prior Malignancy : History of malignancy other than acute lymphoblastic leukemia within 5 years, except for adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer post-radical resection, or ductal carcinoma in situ post-resection.
- •MRD-Negative B-ALL : Standard-risk B-ALL with MRD-negative status pre-transplant (per NCCN 2024.V2).
- •Disease Activity : Relapse of primary disease or CR/MRD positivity (≥0.01%) confirmed by bone marrow re-evaluation within 1 week before maintenance therapy.
- •T-Cell Deficiency : Absolute CD3+ T-cell count ≤0.5×10⁹/L prior to maintenance therapy.
- •Active GVHD : Concurrent acute/chronic GVHD requiring systemic immunosuppressive treatment.
- •Unstable Systemic Diseases : Including but not limited to:
- •Unstable angina or cerebrovascular accident/transient ischemic attack (within 3 months)
- •Myocardial infarction (within 3 months)
- •Congestive heart failure (NYHA Class ≥ III)
- •Post-pacemaker implantation with severe arrhythmia requiring medication
- •Uncontrolled hepatic/renal/metabolic diseases
- •Pulmonary hypertension
- •Active Infection : Uncontrolled infections requiring intravenous antibiotics. HIV : Positive human immunodeficiency virus status. Hepatitis : Active HBV/HCV requiring antiviral therapy.
- •Psychiatric Conditions : Mental disorders or inability to provide informed consent.
- •Substance Abuse : Drug addiction or chronic alcoholism affecting trial evaluation.
- •Reproductive Status :
- •Pregnant/breastfeeding females Fertile patients unwilling to use contraception during treatment and 12 months post-treatment
- •- Other : Conditions deemed inappropriate by investigators.
研究组 & 干预措施
blinatumomab combined with venetoclax as maintenance therapy
blinatumomab combined with venetoclax as maintenance therapy for high-risk Philadelphia chromosome-negative acute B-cell lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation
干预措施: blinatumomab combined with venetoclax as maintenance therapy (Drug)
结局指标
主要结局
the 2-year progression-free survival (PFS) rate post-transplantation
时间窗: the 2-year progression-free survival (PFS) rate post-transplantation
evaluate the 2-year progression-free survival (PFS) rate post-transplantation of blinatumomab combined with venetoclax as maintenance therapy following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients
次要结局
- the 2-year cumulative relapse rate(2 year after allogeneic hematopoietic stem cell transplantation (allo-HSCT))
- 2-year overall survival (OS)(2 year after allogeneic hematopoietic stem cell transplantation (allo-HSCT))
研究者
Xianbo Huang
Principal Investigator
First Affiliated Hospital of Zhejiang University