ABL/JAK Inhibitors With Chemotherapy and Venetoclax for Ph-like ALL
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age14-60
SponsorInstitute of Hematology & Blood Diseases Hospital, China
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Olverembatinib
DrugThird-generation TKI targeting ABL class fusions. 40 mg every other day, continuous throughout all phases except during HD-MTX.
Gecacitinib
DrugJAK1/2 inhibitor targeting JAK pathway alterations. 100 mg twice daily during CAMVT consolidation and maintenance.
Venetoclax
DrugBCL-2 inhibitor. Escalating doses (100→200→400 mg) during induction; 400 mg during maintenance VP cycles.
Chemotherapy Regimen
DrugMulti-agent chemotherapy including vincristine, prednisone, daunorubicin, cyclophosphamide, pegaspargase, cytarabine, 6-MP, MTX, and dexamethasone per protocol phases.
Blinatumomab
DrugOptional CD19-directed BiTE antibody. 28-day continuous infusions alternating with chemotherapy.
CAR-T Cell Therapy
Procedure/SurgeryOptional cellular immunotherapy preceded by fludarabine/cyclophosphamide lymphodepletion.
Allogeneic HSCT
Procedure/SurgeryStem cell transplantation for eligible patients in first complete remission.
Treatment groups
92 Participants
are divided into 2 treatment groupsGroup A: ABL pathway groupExperimental treatment 6 interventions
Group B: JAK pathway groupExperimental treatment 6 interventions
Trial outcomes
Primary outcomes
1
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 initiationSecondary outcomes
1
Complete response (CR) rate
Time frame
At completion of induction therapy2
Rate of next-generation sequencing-MRD (NGS-MRD) negative complete remission at 3 months post-treatment
Time frame
At 3 months after start of treatment3
Overall survival
Time frame
Up to 5 years4
Disease-free survival
Time frame
Up to 5 yearsSponsors and contacts
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Source ClinicalTrials.gov