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

NCT07454226 | Recruiting

• 1 other identifier: IIT2026023
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ph-Like; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

• Overall survival

  Up to 5 years

• Disease-free survival

  Up to 5 years

• Relapse-free survival

  Up to 5 years

Study Arms (2)

ABL pathway group

EXPERIMENTAL

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; Drug: Venetoclax; Drug: Chemotherapy Regimen; Drug: Blinatumomab; Procedure: CAR-T Cell Therapy; Procedure: Allogeneic HSCT

JAK pathway group

EXPERIMENTAL

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: Gecacitinib; Drug: Venetoclax; Drug: Chemotherapy Regimen; Drug: Blinatumomab; Procedure: CAR-T Cell Therapy; Procedure: Allogeneic HSCT

Interventions

Olverembatinib DRUG

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

ABL pathway group

Venetoclax DRUG

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

ABL pathway group; JAK pathway group

Chemotherapy Regimen DRUG

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

ABL pathway group; JAK pathway group

Gecacitinib DRUG

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

JAK pathway group

Blinatumomab DRUG

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

ABL pathway group; JAK pathway group

CAR-T Cell Therapy PROCEDURE

Optional cellular immunotherapy preceded by fludarabine/cyclophosphamide lymphodepletion.

ABL pathway group; JAK pathway group

Allogeneic HSCT PROCEDURE

Stem cell transplantation for eligible patients in first complete remission.

ABL pathway group; JAK pathway group

Eligibility Criteria

• Age: 14 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Blood diseases hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

olverembatinib; venetoclax; Drug Therapy; blinatumomab; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Immunologic Techniques; Investigative Techniques

Central Study Contacts

Hui Wei, MD

CONTACT

13132507161; weihui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 6, 2026
• Study Start: May 30, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)