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

Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Study ID
NCT07454226
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
14 Years - 60 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
May 30, 2026
Status verified
May 2026
Primary completion
Mar 1, 2028
Completion
Mar 1, 2030

Study Design

Enrollment
92 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Experimental: 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.

Primary Outcome Measure

Rate of flow cytometry-minimal residual disease (flow-MRD) negative complete remission at 3 months after treatment initiation [ Time Frame: At 3 months after treatment initiation ]

Central Contacts

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