A Prospective, Umbrella, Phase 2 Study of Immunotargeted Agents Combined With Low-Dose Chemotherapy in Adult Patients With Newly Diagnosed Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Complete Molecular Remission (CMR) Rate After 1 Cycle of Induction Therapy
研究概览
简要总结
This is a prospective, open-label, single-arm, umbrella phase 2 clinical trial enrolling 22 adult patients with newly diagnosed Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL).
As an umbrella trial, all patients share the same target disease (newly diagnosed Ph+ B-ALL) and receive a uniform induction backbone consisting of multi-targeted immunotherapy, targeted therapy, and reduced-intensity chemotherapy. After induction, patients are stratified and assigned to two distinct consolidation pathways based on clinical condition, performance status, resource availability, and patient preference:
Pathway A: Consolidation with CD19-directed CAR-T cell therapy to achieve deep molecular remission; Pathway B: Consolidation with sequential immunochemotherapy to maximize minimal residual disease (MRD) clearance.
A backup chemotherapy backbone is provided for patients ineligible for antibody therapy. All patients, regardless of consolidation pathway, proceed to a unified long-term maintenance regimen. The primary endpoint is the complete molecular remission (CMR) rate after one cycle of induction therapy. MRD is monitored longitudinally by flow cytometry, quantitative PCR, and immune repertoire sequencing. Safety is evaluated per NCI CTCAE version 5.0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Age ≥ 18 years
- •Newly diagnosed, previously untreated Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) confirmed by cytogenetics and/or molecular testing
- •Leukemic blasts expressing CD22
- •Adequate organ function (renal, hepatic, cardiac)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Life expectancy ≥ 3 months
- •Written informed consent obtained prior to any study-related procedures
排除标准
- •Prior systemic anti-leukemic therapy, including chemotherapy, targeted therapy, or immunotherapy
- •History of chronic myeloid leukemia (CML) or other hematologic malignancies
- •Central nervous system (CNS) leukemia or extramedullary disease at diagnosis
- •Uncontrolled active infection or severe comorbidities
- •HIV positivity or known hepatitis B/C infection with active viral replication
- •Pregnant or breastfeeding
- •Inability to comply with study procedures or follow-up requirements
研究组 & 干预措施
Immunotargeted Therapy + Low-Dose Chemotherapy Arm
All patients receive a uniform induction therapy backbone combining targeted therapy, immunotherapy, and reduced-intensity chemotherapy. After induction, patients are stratified into two consolidation pathways based on clinical status: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to a unified long-term maintenance regimen.
干预措施: Inotuzumab Ozogamicin (IO) (Drug)
Immunotargeted Therapy + Low-Dose Chemotherapy Arm
All patients receive a uniform induction therapy backbone combining targeted therapy, immunotherapy, and reduced-intensity chemotherapy. After induction, patients are stratified into two consolidation pathways based on clinical status: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to a unified long-term maintenance regimen.
干预措施: CD19-directed chimeric antigen receptor (CAR-T) T cells (Biological)
Immunotargeted Therapy + Low-Dose Chemotherapy Arm
All patients receive a uniform induction therapy backbone combining targeted therapy, immunotherapy, and reduced-intensity chemotherapy. After induction, patients are stratified into two consolidation pathways based on clinical status: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to a unified long-term maintenance regimen.
干预措施: Blinatumomab (Drug)
Immunotargeted Therapy + Low-Dose Chemotherapy Arm
All patients receive a uniform induction therapy backbone combining targeted therapy, immunotherapy, and reduced-intensity chemotherapy. After induction, patients are stratified into two consolidation pathways based on clinical status: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to a unified long-term maintenance regimen.
干预措施: Venetoclax (Drug)
Immunotargeted Therapy + Low-Dose Chemotherapy Arm
All patients receive a uniform induction therapy backbone combining targeted therapy, immunotherapy, and reduced-intensity chemotherapy. After induction, patients are stratified into two consolidation pathways based on clinical status: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to a unified long-term maintenance regimen.
干预措施: olverembatinib (Drug)
结局指标
主要结局
Complete Molecular Remission (CMR) Rate After 1 Cycle of Induction Therapy
时间窗: At the end of Cycle 1 (each cycle is 28 days, approximately 4 weeks from enrollment)
The proportion of patients achieving complete molecular remission (CMR), defined as undetectable BCR::ABL1 transcript by quantitative PCR (BCR::ABL1/ABL1 ratio \< 0.001%), after 1 cycle of induction therapy.
次要结局
- 3-Month Complete Remission (CR)(3 months after study enrollment)
- 3-Month MRD Negativity Rates(3 months after study enrollment)
- 2-Year Overall Survival (OS)(2 years after the last patient enrollment)
- 2-Year Disease-Free Survival (DFS)(2 years after the last patient enrollment)
- 2-Year Event-Free Survival (EFS)(2 years after the last patient enrollment)
- Incidence of Treatment-Related Adverse Events (TRAEs)(From study enrollment to 60 days after the last treatment)