This is a prospective, open-label, non-randomized cohort study evaluating the efficacy and safety of a pediatric-inspired chemotherapy regimen (IH-2014 based) combined with venetoclax and immunotherapy in adult patients with newly diagnosed Ph-negative Acute Lymphoblastic Leukemia (ALL). Patients aged ≥14years,≤60 years will be enrolled. Treatment includes induction, consolidation, early intensification, delayed intensification, and maintenance phases. The use and number of cycles of immunotherapy will be based on patient preference. The primary endpoint is Event-Free Survival (EFS) and MRD-negative CR rates after induction therapy(by flow cytometry and NGS). Secondary endpoints include Complete Remission (CR) rate, MRD-negative CR rates at 12 weeks (by flow cytometry and NGS), Overall Survival (OS), Relapse-Free Survival (RFS), and cumulative relapse rate.
Adult Ph-negative ALL has inferior outcomes compared to childhood ALL. Pediatric-inspired regimens have improved survival in adolescent and young adult (AYA) patients. Venetoclax, a BCL-2 inhibitor, has shown preclinical sensitivity in Ph-negative ALL. Our center's previous IH-2022 regimen (a pediatric-inspired regimen combined with venetoclax protocol) showed promising efficacy and tolerability in adult patients.Immunotherapy is effective in ALL. This study aims to integrate immunotherapy into the pediatric-inspired backbone to optimize the regimen and improve survival outcomes.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
Includes vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, dexamethasone, cytarabine, 6-mercaptopurine, and high-dose methotrexate.
Monthly MM regimen (6-mercaptopurine and methotrexate) and every 3 months VP (vincristine and prednisone) plus venetoclax.
Optional; 1 to 4 cycles (28 days each) based on patient choice, starting post-induction, alternating with chemotherapy cycles.
Oral targeted therapy administered during induction, consolidation, and maintenance phases as per protocol
Intrathecal injection (methotrexate, cytarabine, dexamethasone) for a total of at least 15 sessions. Prophylactic cranial irradiation (18 Gy) is an alternative for patients unable or unwilling to receive intrathecal injections.
Preconditioning regimen with fludarabine and cyclophosphamide (FC) administered after the third course (second consolidation) for patients receiving CAR-T.
Allogeneic or autologous HSCT considered for high-risk patients or those with positive MRD after induction in CR1, provided a suitable donor is available.
Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGEvent-Free Survival
Time frame: up to 5 years
MRD-negative CR rate by flow cytometry after induction regimen
Time frame: up to 6 weeks
Complete Remission Rate
Time frame: up to 1 year
MRD-negative CR rate by flow cytometry at 12 weeks
Time frame: up to 12 weeks
MRD-negative CR rate by NGS at 12 weeks
Time frame: up to 12 weeks
Overall Survival (OS)
Time frame: Up to 5 years
Relapse-Free Survival (RFS)
Time frame: Up to 5 years
Cumulative Incidence of Relapse
Time frame: Up to 5 years
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