Ph-Like, Acute Lymphoblastic Leukemia
Conditions
Brief summary
This open-label, non-randomized, single-arm, 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 ruxolitinib. 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.
Interventions
Multi-agent chemotherapy including vincristine, prednisone, daunorubicin, cyclophosphamide, pegaspargase, cytarabine, 6-MP, MTX, and dexamethasone per protocol phases.
DRUGBlinatumomab
Optional CD19-directed BiTE antibody. 28-day continuous infusions alternating with chemotherapy.
DRUGVenetoclax
BCL-2 inhibitor. Escalating doses (100→200→400 mg) during induction; 400 mg during maintenance VP cycles.
DRUGOlverembatinib
Third-generation TKI targeting ABL class fusions. 40 mg every other day, continuous throughout all phases except during HD-MTX.
DRUGRuxolitinib
JAK1/2 inhibitor targeting JAK pathway alterations. 100 mg twice daily during CAMVT consolidation and maintenance.
PROCEDURECAR-T Cell Therapy
Optional cellular immunotherapy preceded by fludarabine/cyclophosphamide lymphodepletion.
PROCEDUREAllogeneic HSCT
Stem cell transplantation for eligible patients in first complete remission.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 60-day mortality rate | At 60 days |
| Disease-free survival | Up to 5 years |
| Relapse-free survival | 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 |
| Cumulative incidence of relapse | Up to 5 years |
| Overall survival | Up to 5 years |
Contacts
CONTACTHui Wei, MD
Outcome results
None listed