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

Condition(s) studied

Investigational drug(s) / intervention(s)

Olverembatinib: Third-generation TKI targeting ABL class fusions. 40 mg every other day, continuous throughout all phases except during HD-MTX.

Gecacitinib: JAK1/2 inhibitor targeting JAK pathway alterations. 100 mg twice daily during CAMVT consolidation and maintenance.

Venetoclax: BCL-2 inhibitor. Escalating doses (100→200→400 mg) during induction; 400 mg during maintenance VP cycles.

Chemotherapy Regimen: Multi-agent chemotherapy including vincristine, prednisone, daunorubicin, cyclophosphamide, pegaspargase, cytarabine, 6-MP, MTX, and dexamethasone per protocol phases.

Blinatumomab: Optional CD19-directed BiTE antibody. 28-day continuous infusions alternating with chemotherapy.

CAR-T Cell Therapy: Optional cellular immunotherapy preceded by fludarabine/cyclophosphamide lymphodepletion.

Allogeneic HSCT: Stem cell transplantation for eligible patients in first complete remission.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Rate of flow cytometry-minimal residual disease (flow-MRD) negative complete remission at 3 months after treatment initiation — At 3 months after treatment initiation

Trial sites (1)

On this site

More Institute of Hematology & Blood Diseases Hospital, China trials in China

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