Full-course Immunotherapy Combined With Chemotherapy in Newly Diagnosed B-cell Acute Lymphoblastic Leukemia
The First Affiliated Hospital of Soochow University
101 participants
Apr 1, 2025
INTERVENTIONAL
Conditions
Summary
This is a single-arm, prospective, phase 2 clinical trial evaluating the improvement of survival outcomes of blinatumomab combined with chemotherapy as a full-course treatment regimen in patients with newly diagnosed Philadelphia chromosome-negative (Ph-negative) B-cell precursor acute lymphoblastic leukemia (B-ALL). The study adopts a "reduced-dose chemotherapy + full-course immunotherapy" strategy: induction therapy with reduced-dose chemotherapy combined with blinatumomab to improve remission rate and tolerability; consolidation therapy with alternating Hyper-CVAD (A/B) regimen，blinatumomab and sequential CD19-directed CAR-T therapy to deepen minimal residual disease (MRD) clearance; allogeneic hematopoietic stem cell transplantation (allo-HSCT) for some patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence); and no maintenance therapy. The primary endpoint is 2-year relapse-free survival (RFS). Secondary endpoints include 2-year overall survival (OS), the proportion and time to achieve complete response (CRc), and the proportion and time to achieve minimal residual disease (MRD) negativity. The trial plans to enroll 101 patients aged 15-65 years to demonstrate improved survival outcomes compared with historical controls .
Eligibility
Inclusion Criteria7
- Age ≥15 years and ≤65 years.
- Newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) according to WHO diagnostic criteria, with CD19 expression ≥ 20%
- De novo patients with no prior induction therapy (excluding hydroxyurea and corticosteroid use for ≤ 5 days)
- ECOG performance status score 0-3.
- Liver function: Total bilirubin ≤ 3 times the upper limit of normal (ULN); alanine transaminase (ALT) ≤ 3×ULN; aspartate transaminase (AST) ≤ 3×ULN; (leukemic infiltration is excluded).
- Renal function: Creatinine clearance rate (CrCl) ≥ 30 mL/min
- Able to understand and voluntarily participate in the study, and provide written informed consent
Exclusion Criteria10
- Philadelphia chromosome-positive (Ph+, BCR-ABL1+) ALL
- T-cell acute lymphoblastic leukemia
- Mature B-cell leukemia/lymphoma, B-cell lymphoblastic lymphoma, extramedullary invasion
- Acute mixed phenotype acute leukemia (MPAL)
- Central nervous system (CNS) leukemia
- HIV infection
- Positive HBV-DNA or HCV-RNA
- New York Heart Association (NYHA) functional class ≥ II, or other conditions deemed unsuitable for enrollment by the investigator
- Pregnant or lactating patients
- Patients who refuse to enroll in the study
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Interventions
Induction phase: 9 µg/day on days 8-14, 28 µg/day on days 15-21; If D22 BM not CR/CRi, continue Blinatumomab for next 2 weeks of 28 µg/day; Consolidation phase: 28 µg/day for 28 days.
Reduced-dose induction regimen: Idarubicin 8 mg/m², intravenous, day 1; Vindesine 3 mg/m² (max 4 mg), intravenous, day 1; Dexamethasone 9 mg/m²/day, intravenous, days 1-7. Combined with blinatumomab
Alternating intensive consolidation chemotherapy: Hyper-CVAD-A: Cyclophosphamide ,Vincristine , Doxorubicin , Dexamethasone ; Hyper-CVAD-B: Methotrexate , Cytarabine . Alternated with CD19-CART and blinatumomab
Allogeneic hematopoietic stem cell transplantation, performed after consolidation therapy in patients with KMT2A rearrangement, TP53 mutation, persistent MRD positivity or MRD recurrence
CD19-CART is administered sequentially in the consolidation phase: First infusion : Following the first course of blinatumomab (28 µg/day, IV, days 1-28) before subsequent Hyper-CVAD chemotherapy. Second infusion : After completion of alternating Hyper-CVAD and blinatumomab consolidation cycles.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07564453