Study Summary
This is a prospective, open-label, non-randomized cohort study evaluating the efficacy and safety of a pediatric-inspired chemotherapy regimen (IH-2022 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). 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.
Interventions
VDCLP+VDRUG
Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
2VIPDRUG
Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
Consolidation TherapyDRUG
Includes vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, dexamethasone, cytarabine, 6-mercaptopurine, and high-dose methotrexate.
Maintenance TherapyDRUG
Monthly MM regimen (6-mercaptopurine and methotrexate) and every 3 months VP (vincristine and prednisone) plus venetoclax.
BlinatumomabDRUG
Optional; 1 to 4 cycles (28 days each) based on patient choice, starting post-induction, alternating with chemotherapy cycles.
VenetoclaxDRUG
Oral targeted therapy administered during induction, consolidation, and maintenance phases as per protocol
CNS ProphylaxisPROCEDURE
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.
CAR-T Cell TherapyPROCEDURE
Preconditioning regimen with fludarabine and cyclophosphamide (FC) administered after the third course (second consolidation) for patients receiving CAR-T.
Hematopoietic Stem Cell Transplantation (HSCT)PROCEDURE
Allogeneic or autologous HSCT considered for high-risk patients or those with positive MRD after induction in CR1, provided a suitable donor is available.