NCT07454226

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

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

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 14 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This open-label, non-randomized, single-arm, 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.

Conditions

• Ph-Like
• Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	Olverembatinib	Third-generation TKI targeting ABL class fusions. 40 mg every other day, continuous throughout all phases except during HD-MTX.
DRUG	Gecacitinib	JAK1/2 inhibitor targeting JAK pathway alterations. 100 mg twice daily during CAMVT consolidation and maintenance.
DRUG	Venetoclax	BCL-2 inhibitor. Escalating doses (100→200→400 mg) during induction; 400 mg during maintenance VP cycles.
DRUG	Chemotherapy Regimen	Multi-agent chemotherapy including vincristine, prednisone, daunorubicin, cyclophosphamide, pegaspargase, cytarabine, 6-MP, MTX, and dexamethasone per protocol phases.
DRUG	Blinatumomab	Optional CD19-directed BiTE antibody. 28-day continuous infusions alternating with chemotherapy.
PROCEDURE	CAR-T Cell Therapy	Optional cellular immunotherapy preceded by fludarabine/cyclophosphamide lymphodepletion.
PROCEDURE	Allogeneic HSCT	Stem cell transplantation for eligible patients in first complete remission.

Timeline

• Start date: 2026-04-30
• Primary completion: 2028-03-01
• Completion: 2030-03-01
• First posted: 2026-03-06
• Last updated: 2026-04-16