Full-course Immunotherapy Combined With Chemotherapy in Newly Diagnosed B-cell Acute Lymphoblastic Leukemia

Phase 2RecruitingNCT07564453

The First Affiliated Hospital of Soochow University101 enrolled

Overview

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 .

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

101

Conditions

B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative

Interventions

BlinatumomabBIOLOGICAL

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.

Induction ChemotherapyDRUG

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

Hyper-CVADDRUG

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 transplantationPROCEDURE

Allogeneic hematopoietic stem cell transplantation, performed after consolidation therapy in patients with KMT2A rearrangement, TP53 mutation, persistent MRD positivity or MRD recurrence

CAR-T cell therapyBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 15 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥15 years and ≤65 years. 2. Newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) according to WHO diagnostic criteria, with CD19 expression ≥ 20% 3. De novo patients with no prior induction therapy (excluding hydroxyurea and corticosteroid use for ≤ 5 days) 4. ECOG performance status score 0-3. 5. 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). 6. Renal function: Creatinine clearance rate (CrCl) ≥ 30 mL/min 7. Able to understand and voluntarily participate in the study, and provide written informed consent Exclusion Criteria: 1. Philadelphia chromosome-positive (Ph+, BCR-ABL1+) ALL 2. T-cell acute lymphoblastic leukemia 3. Mature B-cell leukemia/lymphoma, B-cell lymphoblastic lymphoma, extramedullary invasion 4. Acute mixed phenotype acute leukemia (MPAL) 5. Central nervous system (CNS) leukemia 6. HIV infection 7. Positive HBV-DNA or HCV-RNA 8. New York Heart Association (NYHA) functional class ≥ II, or other conditions deemed unsuitable for enrollment by the investigator 9. Pregnant or lactating patients 10. Patients who refuse to enroll in the study

Outcomes

Primary Outcomes

2-year relapse-free survival (RFS)

Defined as the time from enrollment to relapse, death from any cause, or last follow-up, whichever occurs first.

Time frame: From enrollment through 2 years post-last patient enrolled

Secondary Outcomes

2-year overall survival (OS)

Defined as the time from enrollment to death from any cause or last follow-up, whichever occurs first.

Time frame: From enrollment through 2 years post-last patient enrolled

Composite Complete Remission (CR/CRi) Rate after Induction Therapy

Proportion of patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction phase.CRc is evaluated at: 1) Day 22 after initial induction therapy; 2) After re-induction with blinatumomab for 2 weeks (for patients not achieving CRc at Day 22)

Time frame: From randomization to 2 cycles of induction before consolidation therapy(100 days)

Minimal Residual Disease (MRD) Negativity Rate

Proportion of patients achieving MRD negativity (detected by next-generation sequencing, NGS, sensitivity ≥10-⁵) at multiple time points: after first Hyper-CVAD-B chemotherapy, after second Hyper-CVAD-B chemotherapy, and after CD19-CART2 therapy. MRD negativity is defined as \<10-⁵ leukemic blasts in bone marrow.