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

May 10, 2026 updated by: Institute of Hematology & Blood Diseases Hospital, China

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

92

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300020
        • Recruiting
        • Blood Diseases Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Olverembatinib
Third-generation TKI targeting ABL class fusions. 40 mg every other day, continuous throughout all phases except during HD-MTX.
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.
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.
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.
Drug: Gecacitinib
JAK1/2 inhibitor targeting JAK pathway alterations. 100 mg twice daily during CAMVT consolidation and maintenance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
At 3 months after treatment initiation

Secondary Outcome Measures

Outcome Measure
Time Frame
Relapse-free survival
Time Frame: Up to 5 years
Up to 5 years
Overall survival
Time Frame: Up to 5 years
Up to 5 years
Disease-free survival
Time Frame: Up to 5 years
Up to 5 years
Cumulative incidence of relapse
Time Frame: Up to 5 years
Up to 5 years
Complete response (CR) rate
Time Frame: At completion of induction therapy
At completion of induction therapy
Rate of next-generation sequencing-MRD (NGS-MRD) negative complete remission at 3 months post-treatment
Time Frame: At 3 months after start of treatment
At 3 months after start of treatment
60-day mortality rate
Time Frame: At 60 days
At 60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 30, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2030

Study Registration Dates

First Submitted

February 26, 2026

First Submitted That Met QC Criteria

March 3, 2026

First Posted (Actual)

March 6, 2026

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 10, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2026023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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