Efficacy and Safety of Low-dose Chemotherapy Combined With Immuno-targeted Drugs in Newly Diagnosed Adult Patients With Ph-negative B-cell Acute Lymphocytic Leukemia: A Prospective, Single-arm Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- MRD-negative complete remission rate measured by flow cytometry.
研究概览
简要总结
In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) among adult patients, therapeutic outcomes remain suboptimal despite advances in chemotherapy and immunotherapy. A subset of adults with Ph- B-ALL have comorbidities or physiological limitations that preclude the safe administration of intensive regimens. In recent years, tumor immunotherapy has demonstrated promising safety and efficacy profiles in refractory or relapsed Ph- B-ALL across a wide spectrum of adult ages. These findings suggest that broader application of immunotherapy may represent a critical strategy to improve survival in this population. In this study, we propose a regimen that combines immuno-targeted agents with low-intensity chemotherapy for newly diagnosed adult patients with Ph- B-ALL. Our primary objective is to increase the rate of measurable residual disease (MRD)-negative complete remission (CR) following induction therapy, reduce the risk of relapse, and ultimately enhance overall survival.
详细描述
In this open-label, single-arm, Phase II study, prospective clinical trial, a total of 53 Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) patients will be enrolled. The primary endpoint is measurable residual disease (MRD)-negative complete remission (CR) rate after induction therapy.
The first cycle of induction therapy is administered with Inotuzumab ozogamicin (INO), Venetoclax (VEN), and a combination of low-dose chemotherapy. The second cycle of induction therapy is Blinatumomab (Blino) plus VEN regimen. Alternatively, the first cycle of induction therapy is a combination of VEN and low-dose chemotherapy, and the second cycle of induction therapy is methotrexate (MTX) plus cytarabine (Ara-C) plus VEN regimen. Subsequent consolidation and maintenance therapy consist of low-dose chemotherapy, Blino, and VEN. Patients can receive chimeric antigen receptor T-Cell (CAR-T) Immunotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) or receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. Study patients are scheduled for follow-up for at least 5 years after the end of maintenance therapy.
The purpose of current study is to determine the efficacy and safety of low-dose chemotherapy combined with immuno-targeted drugs in newly diagnosed adult patients with Ph- B-ALL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia according to World Health Organization (WHO) 2016 criteria
- •CD22 positive tumor cells
- •≥18 years of age
- •Estimated survival ≥3 months
- •Consent and effective contraception for men and women of childbearing potential
- •Understanding and signing of informed consent forms and agreement to comply with study requirements.
排除标准
- •Burkitt lymphoma/leukemia
- •acute leukemias of ambiguous lineage
- •pregnant women
- •severe uncontrolled active infection
- •previous history of chronic liver disease (e.g. cirrhosis) or venous occlusive liver disease (VOD) or sinus obstruction syndrome (SOS)
- •History of clinically significant ventricular arrhythmia, syncope of unknown origin (not vasovagal) or sinoatrial block or higher degree atrioventricular (AV) block Chronic bradycardia state (unless permanent pacemaker implanted)
- •New or chronic hepatitis B or C infection (positive for hepatitis B surface antigen and anti-hepatitis C antibody, respectively) or known HIV seropositivity. HIV testing may need to be performed according to local regulations or practices
- •Psychiatric disorders likely to prevent the subject from completing treatment or informed consent
- •Other conditions considered unsuitable for the study by the investigator.
研究组 & 干预措施
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Vincristine (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Cyclophosphamide (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Dexamethasone (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Venetoclax (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Inotuzumab ozogamicin (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Blinatumomab (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: 6-mercaptopurine (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Methotrexate (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Cytarabine (Drug)
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
干预措施: Prednisone (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Vincristine (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Cyclophosphamide (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Dexamethasone (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Venetoclax (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: 6-mercaptopurine (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Methotrexate (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Cytarabine (Drug)
low-dose chemotherapy combined with Venetoclax
The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.
干预措施: Prednisone (Drug)
结局指标
主要结局
MRD-negative complete remission rate measured by flow cytometry.
时间窗: After induction (4 week)
No immature cells were detected by flow cytometry when CR criteria were met after induction therapy.
次要结局
- Complete remission (CR) rate(an expected average of 3 months)
- Overall survival (OS)(Up to 5 years post-registration)
- Relapse free survival (RFS)(Up to 5 years post-registration)
- Disease-free Survival (DFS)(Up to 5 years post-registration)
- Mortality(Day 30 and Day 60 of induction therapy initiation)