An Open-Label, Single-Arm, Phase II Exploratory Study of ABL and JAK Kinase Inhibitors With Chemotherapy and Venetoclax in Adult Patients With Ph-like ALL
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Rate of flow cytometry-minimal residual disease (flow-MRD) negative complete remission at 3 months after treatment initiation
研究概览
简要总结
This open-label, non-randomized, phase II exploratory study aims to evaluate the efficacy and safety of combining pathway-specific tyrosine kinase inhibitors with chemotherapy and venetoclax in patients with newly diagnosed Ph-like acute lymphoblastic leukemia (ALL). Patients are stratified by genetic alteration: those with ABL class fusions (ABL1, ABL2, PDGFRA, PDGFRB) receive olverembatinib, while those with JAK pathway alterations (CRLF2 rearrangement, JAK mutation/fusion, EPOR fusion, SH2B3 deletion, IL7R mutation) receive Gecacitinib. Both groups undergo sequential induction, consolidation, intensification, and maintenance therapy as per protocol.
The primary endpoint is the rate of flow cytometry minimal residual disease (MRD)-negative complete remission (CR MRD-) at 3 months after induction therapy. Secondary endpoints include overall complete remission rate, NGS MRD-negative CR rate at 3 months, overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), cumulative incidence of relapse, and 60-day mortality.
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
- •Age ≥14 years and ≤60 years, regardless of gender
- •ECOG performance status score ≤2
- •Male and female participants of childbearing potential agree to and adopt effective contraceptive measures
- •Criteria for major organ function assessment: total bilirubin <1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN; serum creatinine <2 × ULN; myocardial enzymes <2 × ULN; serum amylase ≤1.5 × ULN; left ventricular ejection fraction (LVEF) >45% as shown by cardiac ultrasound
排除标准
- •Pregnant women
- •Severe uncontrolled active infections
- •Mental illnesses that may hinder the completion of treatment or informed consent
- •Other conditions deemed unsuitable for this study by the investigator
研究组 & 干预措施
ABL pathway group
Patients with ABL class fusions receive olverembatinib combined with chemotherapy and venetoclax. Induction (VOVP): vincristine days 1,8,15,22; prednisone days 1-28; venetoclax days 1-28; olverembatinib every other day days 1-28. Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; olverembatinib every other day days 1-28 for 2 cycles. Subsequent therapy: HD-MTX (days 1,14; olverembatinib withheld); ID-AraC (days 1-3); VPO (vincristine days 1,8; prednisone days 1-14; olverembatinib every other day); repeat HD-MTX; repeat ID-AraC; COAP (cyclophosphamide day 1; vincristine day 1; cytarabine days 1-7; prednisone days 1-7). Maintenance: alternating MM (6-MP/MTX) and VP + venetoclax, with continuous olverembatinib.
干预措施: CAR-T Cell Therapy (Procedure)
ABL pathway group
Patients with ABL class fusions receive olverembatinib combined with chemotherapy and venetoclax. Induction (VOVP): vincristine days 1,8,15,22; prednisone days 1-28; venetoclax days 1-28; olverembatinib every other day days 1-28. Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; olverembatinib every other day days 1-28 for 2 cycles. Subsequent therapy: HD-MTX (days 1,14; olverembatinib withheld); ID-AraC (days 1-3); VPO (vincristine days 1,8; prednisone days 1-14; olverembatinib every other day); repeat HD-MTX; repeat ID-AraC; COAP (cyclophosphamide day 1; vincristine day 1; cytarabine days 1-7; prednisone days 1-7). Maintenance: alternating MM (6-MP/MTX) and VP + venetoclax, with continuous olverembatinib.
干预措施: Allogeneic HSCT (Procedure)
JAK pathway group
Patients with JAK pathway alterations receive Gecacitinib combined with chemotherapy and venetoclax. Induction (VDCLP+V): vincristine days 1,8,15,22; daunorubicin days 1-3; cyclophosphamide days 1,15; pegaspargase day 5; prednisone days 1-28; venetoclax days 6-14 (may extend to day 21). Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; vincristine day 1; ruxolitinib 100 mg twice daily days 1-28 for 2 cycles. Subsequent therapy (ruxolitinib withheld): early intensification (HVL), delayed intensification (VDLD then CAMVL), repeated once. Maintenance: alternating MM and VP + venetoclax, with continuous ruxolitinib.
干预措施: CAR-T Cell Therapy (Procedure)
JAK pathway group
Patients with JAK pathway alterations receive Gecacitinib combined with chemotherapy and venetoclax. Induction (VDCLP+V): vincristine days 1,8,15,22; daunorubicin days 1-3; cyclophosphamide days 1,15; pegaspargase day 5; prednisone days 1-28; venetoclax days 6-14 (may extend to day 21). Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; vincristine day 1; ruxolitinib 100 mg twice daily days 1-28 for 2 cycles. Subsequent therapy (ruxolitinib withheld): early intensification (HVL), delayed intensification (VDLD then CAMVL), repeated once. Maintenance: alternating MM and VP + venetoclax, with continuous ruxolitinib.
干预措施: Allogeneic HSCT (Procedure)
JAK pathway group
Patients with JAK pathway alterations receive Gecacitinib combined with chemotherapy and venetoclax. Induction (VDCLP+V): vincristine days 1,8,15,22; daunorubicin days 1-3; cyclophosphamide days 1,15; pegaspargase day 5; prednisone days 1-28; venetoclax days 6-14 (may extend to day 21). Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; vincristine day 1; ruxolitinib 100 mg twice daily days 1-28 for 2 cycles. Subsequent therapy (ruxolitinib withheld): early intensification (HVL), delayed intensification (VDLD then CAMVL), repeated once. Maintenance: alternating MM and VP + venetoclax, with continuous ruxolitinib.
干预措施: Gecacitinib (Drug)
JAK pathway group
Patients with JAK pathway alterations receive Gecacitinib combined with chemotherapy and venetoclax. Induction (VDCLP+V): vincristine days 1,8,15,22; daunorubicin days 1-3; cyclophosphamide days 1,15; pegaspargase day 5; prednisone days 1-28; venetoclax days 6-14 (may extend to day 21). Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; vincristine day 1; ruxolitinib 100 mg twice daily days 1-28 for 2 cycles. Subsequent therapy (ruxolitinib withheld): early intensification (HVL), delayed intensification (VDLD then CAMVL), repeated once. Maintenance: alternating MM and VP + venetoclax, with continuous ruxolitinib.
干预措施: Blinatumomab (Drug)
ABL pathway group
Patients with ABL class fusions receive olverembatinib combined with chemotherapy and venetoclax. Induction (VOVP): vincristine days 1,8,15,22; prednisone days 1-28; venetoclax days 1-28; olverembatinib every other day days 1-28. Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; olverembatinib every other day days 1-28 for 2 cycles. Subsequent therapy: HD-MTX (days 1,14; olverembatinib withheld); ID-AraC (days 1-3); VPO (vincristine days 1,8; prednisone days 1-14; olverembatinib every other day); repeat HD-MTX; repeat ID-AraC; COAP (cyclophosphamide day 1; vincristine day 1; cytarabine days 1-7; prednisone days 1-7). Maintenance: alternating MM (6-MP/MTX) and VP + venetoclax, with continuous olverembatinib.
干预措施: Olverembatinib (Drug)
ABL pathway group
Patients with ABL class fusions receive olverembatinib combined with chemotherapy and venetoclax. Induction (VOVP): vincristine days 1,8,15,22; prednisone days 1-28; venetoclax days 1-28; olverembatinib every other day days 1-28. Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; olverembatinib every other day days 1-28 for 2 cycles. Subsequent therapy: HD-MTX (days 1,14; olverembatinib withheld); ID-AraC (days 1-3); VPO (vincristine days 1,8; prednisone days 1-14; olverembatinib every other day); repeat HD-MTX; repeat ID-AraC; COAP (cyclophosphamide day 1; vincristine day 1; cytarabine days 1-7; prednisone days 1-7). Maintenance: alternating MM (6-MP/MTX) and VP + venetoclax, with continuous olverembatinib.
干预措施: Venetoclax (Drug)
ABL pathway group
Patients with ABL class fusions receive olverembatinib combined with chemotherapy and venetoclax. Induction (VOVP): vincristine days 1,8,15,22; prednisone days 1-28; venetoclax days 1-28; olverembatinib every other day days 1-28. Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; olverembatinib every other day days 1-28 for 2 cycles. Subsequent therapy: HD-MTX (days 1,14; olverembatinib withheld); ID-AraC (days 1-3); VPO (vincristine days 1,8; prednisone days 1-14; olverembatinib every other day); repeat HD-MTX; repeat ID-AraC; COAP (cyclophosphamide day 1; vincristine day 1; cytarabine days 1-7; prednisone days 1-7). Maintenance: alternating MM (6-MP/MTX) and VP + venetoclax, with continuous olverembatinib.
干预措施: Blinatumomab (Drug)
ABL pathway group
Patients with ABL class fusions receive olverembatinib combined with chemotherapy and venetoclax. Induction (VOVP): vincristine days 1,8,15,22; prednisone days 1-28; venetoclax days 1-28; olverembatinib every other day days 1-28. Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; olverembatinib every other day days 1-28 for 2 cycles. Subsequent therapy: HD-MTX (days 1,14; olverembatinib withheld); ID-AraC (days 1-3); VPO (vincristine days 1,8; prednisone days 1-14; olverembatinib every other day); repeat HD-MTX; repeat ID-AraC; COAP (cyclophosphamide day 1; vincristine day 1; cytarabine days 1-7; prednisone days 1-7). Maintenance: alternating MM (6-MP/MTX) and VP + venetoclax, with continuous olverembatinib.
干预措施: Chemotherapy Regimen (Drug)
JAK pathway group
Patients with JAK pathway alterations receive Gecacitinib combined with chemotherapy and venetoclax. Induction (VDCLP+V): vincristine days 1,8,15,22; daunorubicin days 1-3; cyclophosphamide days 1,15; pegaspargase day 5; prednisone days 1-28; venetoclax days 6-14 (may extend to day 21). Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; vincristine day 1; ruxolitinib 100 mg twice daily days 1-28 for 2 cycles. Subsequent therapy (ruxolitinib withheld): early intensification (HVL), delayed intensification (VDLD then CAMVL), repeated once. Maintenance: alternating MM and VP + venetoclax, with continuous ruxolitinib.
干预措施: Chemotherapy Regimen (Drug)
JAK pathway group
Patients with JAK pathway alterations receive Gecacitinib combined with chemotherapy and venetoclax. Induction (VDCLP+V): vincristine days 1,8,15,22; daunorubicin days 1-3; cyclophosphamide days 1,15; pegaspargase day 5; prednisone days 1-28; venetoclax days 6-14 (may extend to day 21). Consolidation (CAMVT): cyclophosphamide day 1; cytarabine days 1,2,8,9; 6-MP days 1-7; vincristine day 1; ruxolitinib 100 mg twice daily days 1-28 for 2 cycles. Subsequent therapy (ruxolitinib withheld): early intensification (HVL), delayed intensification (VDLD then CAMVL), repeated once. Maintenance: alternating MM and VP + venetoclax, with continuous ruxolitinib.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Rate of flow cytometry-minimal residual disease (flow-MRD) negative complete remission at 3 months after treatment initiation
时间窗: At 3 months after treatment initiation
次要结局
- 60-day mortality rate(At 60 days)
- Complete response (CR) rate(At completion of induction therapy)
- Rate of next-generation sequencing-MRD (NGS-MRD) negative complete remission at 3 months post-treatment(At 3 months after start of treatment)
- Overall survival(Up to 5 years)
- Disease-free survival(Up to 5 years)
- Relapse-free survival(Up to 5 years)
- Cumulative incidence of relapse(Up to 5 years)