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

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: Acute Lymphoblastic Leukemia; Ph-Like
• Intervention / Treatment: Drug: Olverembatinib; Drug: Venetoclax; Drug: Chemotherapy Regimen; Drug: Blinatumomab; Procedure: CAR-T Cell Therapy; Procedure: Allogeneic HSCT; Drug: Gecacitinib

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Wei, MD; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Blood Diseases Hospital
      • Contact: Hui Wei; Phone Number: 022-23608456; Email: weihui@ihcams.ac.cn

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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	At 3 months after treatment initiation

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

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: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; venetoclax; blinatumomab; Drug Therapy; Immunotherapy, Adoptive; olverembatinib
• 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