Ph- Acute Lymphoblastic Leukemia (Ph-ALL)
Conditions
Brief summary
This is a prospective, open-label, single-arm, umbrella phase 2 clinical trial enrolling 32 adult patients with newly diagnosed Philadelphia chromosome-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL). All patients receive a frontline treatment backbone consisting of low-dose chemotherapy combined with immuno-targeted agents and a BCL2 inhibitor. Subsequent treatment pathways are guided by MRD response, disease characteristics, and clinical decision-making, including antibody-based immunotherapy, CAR-T cell therapy, or hematopoietic stem cell transplantation. All patients continue protocol-defined maintenance therapy after consolidation. The primary endpoint is the complete remission rate with negative flow cytometric MRD after induction therapy. MRD is monitored longitudinally by flow cytometry, quantitative PCR, and immune repertoire sequencing. Safety is evaluated according to NCI CTCAE version 5.0.
Interventions
Anti-CD22 antibody-drug conjugate (ADC) administered intravenously during induction and consolidation therapy.
DRUGVenetoclax
BCL-2 inhibitor administered orally daily during induction and consolidation cycles to enhance leukemic cell apoptosis.
DRUGBlinatumomab
CD19/CD3 bispecific T-cell engager (BiTE) administered as continuous intravenous infusion during consolidation therapy.
BIOLOGICALCD19-directed chimeric antigen receptor (CAR-T) T cells
Autologous CD19 CAR-T cell therapy administered as a single intravenous infusion as optional consolidation therapy for eligible patients.
DRUGVincristine
A vinca alkaloid that inhibits microtubule formation by binding to tubulin, resulting in mitotic arrest and inhibition of proliferation of rapidly dividing leukemic cells.
DRUGCyclophosphamide
An alkylating agent that forms DNA cross-links, leading to inhibition of DNA replication and transcription and subsequent apoptosis of rapidly proliferating hematopoietic cells.
DRUGDexamethasone
A synthetic glucocorticoid that induces lymphoid cell apoptosis and exerts anti-inflammatory and immunosuppressive effects, contributing to reduction of leukemic burden.
DRUGMethotrexate
A folate antimetabolite that inhibits dihydrofolate reductase, resulting in impaired DNA synthesis and cell replication, particularly in rapidly dividing lymphoid cells.
A pyrimidine nucleoside analog that inhibits DNA polymerase, leading to termination of DNA chain elongation and inhibition of leukemic cell proliferation.
DRUGPrednisone
A glucocorticoid that induces apoptosis in lymphoid cells and provides anti-inflammatory and immunosuppressive effects as part of multi-agent leukemia therapy.
A purine analog antimetabolite that interferes with purine nucleotide synthesis and incorporates into DNA and RNA, inhibiting nucleic acid synthesis and cell proliferation.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed adult (≥18 years) patients with Ph-negative B-cell acute lymphoblastic leukemia according to WHO 2022 criteria. 2. CD22-positive expression on tumor cells (CD22 ≥20%). 3. Expected survival ≥3 months. 4. Sexually active men and women of childbearing potential must agree to use effective contraception. 5. Ability to understand and voluntarily sign informed consent, and willingness to comply with study requirements. Informed consent must be signed by the patient or a legal next of kin prior to initiation of any study-specific procedures.
Exclusion criteria
1. Burkitt lymphoma/leukemia. 2. Acute leukemia of ambiguous lineage. 3. Pregnant women. 4. Severe, uncontrolled active infections. 5. History of chronic liver disease (e.g., liver cirrhosis) or prior veno-occlusive disease (VOD) / sinusoidal obstruction syndrome (SOS). 6. History of clinically significant ventricular arrhythmias, unexplained syncope (not vasovagal), or sinus node dysfunction or high-grade atrioventricular (AV) block with chronic bradycardia, unless a permanent pacemaker has been implanted. 7. Uncontrolled active hepatitis B or hepatitis C infection, or known HIV seropositivity. HIV testing may be required according to local regulations or standards. 8. Psychiatric disorders that may impair the subject's ability to complete treatment or provide informed consent. 9. Any other conditions deemed by the investigator to render the subject unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow Cytometric MRD-Negative Complete Remission Rate | At the end of induction therapy (approximately 1 month after treatment initiation) | Proportion of patients achieving complete remission (CR) with negative measurable residual disease (MRD) assessed by multiparameter flow cytometry after completion of induction therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Next-Generation Sequencing (NGS)-MRD Negative Remission Rate | Within 3 months after treatment initiation | Proportion of patients achieving MRD-negative remission assessed by immune repertoire sequencing. |
| Best MRD Clearance Rate | Within 3 months after treatment initiation | Proportion of patients achieving the deepest MRD response during the first 3 months of treatment as assessed by flow cytometry, quantitative PCR, or immune repertoire sequencing. |
| Overall Survival (OS) | Up to 5 years | Time from study enrollment to death from any cause. |
| Disease-Free Survival (DFS) | Up to 5 years | Time from achievement of complete remission to relapse or death from any cause. |
| Relapse-Free Survival (RFS) | Up to 5 years | Time from achievement of MRD-negative remission to hematologic relapse or death. |
| 30-Day Mortality | 30 days | Proportion of patients who die from any cause within 30 days after treatment initiation. |
| 60-Day Mortality | 60 days | Proportion of patients who die from any cause within 60 days after treatment initiation. |
| Incidence of Adverse Events | From treatment initiation through completion of study treatment, up to 5 years | Frequency, severity, and type of adverse events graded according to the National Cancer |
Contacts
CONTACTYing Wang, MD, PhD
Outcome results
None listed