Ph+ Acute Lymphoblastic Leukemia (Ph+ALL)
Conditions
Brief summary
This is a prospective, open-label, single-arm, umbrella phase 2 clinical trial enrolling 22 adult patients with newly diagnosed Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL). As an umbrella trial, all patients share the same target disease (newly diagnosed Ph+ B-ALL) and receive a uniform induction backbone consisting of multi-targeted immunotherapy, targeted therapy, and reduced-intensity chemotherapy. After induction, patients are stratified and assigned to two distinct consolidation pathways based on clinical condition, performance status, resource availability, and patient preference: Pathway A: Consolidation with CD19-directed CAR-T cell therapy to achieve deep molecular remission; Pathway B: Consolidation with sequential immunochemotherapy to maximize minimal residual disease (MRD) clearance. A backup chemotherapy backbone is provided for patients ineligible for antibody therapy. All patients, regardless of consolidation pathway, proceed to a unified long-term maintenance regimen. The primary endpoint is the complete molecular remission (CMR) rate after one cycle of induction therapy. MRD is monitored longitudinally by flow cytometry, quantitative PCR, and immune repertoire sequencing. Safety is evaluated per NCI CTCAE version 5.0.
Interventions
Anti-CD22 antibody-drug conjugate (ADC) administered intravenously during induction and consolidation therapy.
DRUGBlinatumomab
CD19/CD3 bispecific T-cell engager (BiTE) administered as continuous intravenous infusion during consolidation therapy.
Autologous CD19 CAR-T cell therapy administered as a single intravenous infusion as optional consolidation therapy for eligible patients.
DRUGolverembatinib
Third-generation tyrosine kinase inhibitor (TKI) targeting BCR::ABL1, administered orally daily as part of induction, consolidation, and maintenance therapy.
DRUGVenetoclax
BCL-2 inhibitor administered orally daily during induction and consolidation cycles to enhance leukemic cell apoptosis.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an umbrella trial with a sequential treatment design. All patients receive a uniform induction therapy backbone, then are stratified into two consolidation pathways based on clinical status and patient preference: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to the same maintenance phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Newly diagnosed, previously untreated Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) confirmed by cytogenetics and/or molecular testing * Leukemic blasts expressing CD22 * Adequate organ function (renal, hepatic, cardiac) * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Life expectancy ≥ 3 months * Written informed consent obtained prior to any study-related procedures
Exclusion criteria
* Prior systemic anti-leukemic therapy, including chemotherapy, targeted therapy, or immunotherapy * History of chronic myeloid leukemia (CML) or other hematologic malignancies * Central nervous system (CNS) leukemia or extramedullary disease at diagnosis * Uncontrolled active infection or severe comorbidities * HIV positivity or known hepatitis B/C infection with active viral replication * Pregnant or breastfeeding * Inability to comply with study procedures or follow-up requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Molecular Remission (CMR) Rate After 1 Cycle of Induction Therapy | At the end of Cycle 1 (each cycle is 28 days, approximately 4 weeks from enrollment) | The proportion of patients achieving complete molecular remission (CMR), defined as undetectable BCR::ABL1 transcript by quantitative PCR (BCR::ABL1/ABL1 ratio \< 0.001%), after 1 cycle of induction therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-Month Complete Remission (CR) | 3 months after study enrollment | — |
| 3-Month MRD Negativity Rates | 3 months after study enrollment | — |
| 2-Year Overall Survival (OS) | 2 years after the last patient enrollment | OS is defined as the time from study enrollment to death from any cause. |
| 2-Year Disease-Free Survival (DFS) | 2 years after the last patient enrollment | DFS is defined as the time from study enrollment to disease relapse or death from any cause. |
| 2-Year Event-Free Survival (EFS) | 2 years after the last patient enrollment | EFS is defined as the time from study enrollment to first occurrence of predefined adverse events, disease progression or death. |
| Incidence of Treatment-Related Adverse Events (TRAEs) | From study enrollment to 60 days after the last treatment | Number and severity of adverse events graded according to NCI CTCAE version 5.0. |
Countries
China
Contacts
CONTACTYing Wang, MD, PhD
Outcome results
None listed