A Prospective Cohort Study of a Pediatric-Inspired Chemotherapy Regimen Combined With Venetoclax and Immunotherapy for the Treatment of Adult Ph-Negative Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- MRD-negative CR rate by flow cytometry after induction regimen
研究概览
简要总结
This is a prospective, open-label, non-randomized cohort study evaluating the efficacy and safety of a pediatric-inspired chemotherapy regimen (IH-2014 based) combined with venetoclax and immunotherapy in adult patients with newly diagnosed Ph-negative Acute Lymphoblastic Leukemia (ALL). Patients aged ≥14years,≤60 years will be enrolled. Treatment includes induction, consolidation, early intensification, delayed intensification, and maintenance phases. The use and number of cycles of immunotherapy will be based on patient preference. The primary endpoint is Event-Free Survival (EFS) and MRD-negative CR rates after induction therapy(by flow cytometry and NGS). Secondary endpoints include Complete Remission (CR) rate, MRD-negative CR rates at 12 weeks (by flow cytometry and NGS), Overall Survival (OS), Relapse-Free Survival (RFS), and cumulative relapse rate.
详细描述
Adult Ph-negative ALL has inferior outcomes compared to childhood ALL. Pediatric-inspired regimens have improved survival in adolescent and young adult (AYA) patients. Venetoclax, a BCL-2 inhibitor, has shown preclinical sensitivity in Ph-negative ALL. Our center's previous IH-2022 regimen (a pediatric-inspired regimen combined with venetoclax protocol) showed promising efficacy and tolerability in adult patients.Immunotherapy is effective in ALL. This study aims to integrate immunotherapy into the pediatric-inspired backbone to optimize the regimen and improve survival outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed, previously untreated (except prednisone/hydroxyurea) Ph-negative ALL
- •Age ≥14 years, ≤60 years
- •ECOG performance status ≤2
- •Adequate organ function (liver, kidney, cardiac)
- •For patients of childbearing potential: use of effective contraception
- •Willing and able to provide informed consent
排除标准
- •Burkitt leukemia/lymphoma
- •Acute leukemia of ambiguous lineage
- •Pregnancy or lactation
- •Severe uncontrolled active infection
- •History of pancreatitis
- •Uncontrolled diabetes (HbA1c >7.5%)
- •Active gastrointestinal bleeding within 6 months
- •Arterial/venous thrombosis within 6 months
- •Known HIV positivity
- •Severe psychiatric illness hindering compliance
- •Any other condition deemed unsuitable by the investigator
研究组 & 干预措施
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: CNS Prophylaxis (Procedure)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: 2VIP (Drug)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: CNS Prophylaxis (Procedure)
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: VDCLP+V (Drug)
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Venetoclax (Drug)
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Consolidation Therapy (Drug)
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Maintenance Therapy (Drug)
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Consolidation Therapy (Drug)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Maintenance Therapy (Drug)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Venetoclax (Drug)
Immunotherapy induction Arm
Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Blinatumomab (Drug)
Chemotherapy induction Arm
Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen.
Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate.
Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles.
Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months.
CNS Prophylaxis
Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
MRD-negative CR rate by flow cytometry after induction regimen
时间窗: up to 6 weeks
Event-Free Survival
时间窗: up to 5 years
次要结局
- Complete Remission Rate(up to 1 year)
- MRD-negative CR rate by flow cytometry at 12 weeks(up to 12 weeks)
- MRD-negative CR rate by NGS at 12 weeks(up to 12 weeks)
- Overall Survival (OS)(Up to 5 years)
- Relapse-Free Survival (RFS)(Up to 5 years)
- Cumulative Incidence of Relapse(Up to 5 years)