ABL/JAK Inhibitors With Chemotherapy and Venetoclax for Ph-like ALL

Institute of Hematology & Blood Diseases Hospital, China

Status: Enrolling

Conditions: Acute Lymphoblastic Leukemia; Ph-Like

Treatments: Procedure: CAR-T Cell Therapy; Drug: Olverembatinib; Procedure: Allogeneic HSCT; Drug: Blinatumomab; Drug: Gecacitinib; Drug: Chemotherapy Regimen; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT07454226

IIT2026023

Details and patient eligibility

About

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.

Enrollment: 92 estimated patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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92 participants in 2 patient groups

ABL pathway group

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: Chemotherapy Regimen

Drug: Blinatumomab

Procedure: Allogeneic HSCT

Drug: Olverembatinib

Procedure: CAR-T Cell Therapy

JAK pathway group

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: Chemotherapy Regimen

Drug: Gecacitinib

Drug: Blinatumomab

Procedure: Allogeneic HSCT

Procedure: CAR-T Cell Therapy