Acute Lymphoblastic Leukemia, Adult
Conditions
Brief 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.
Detailed description
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 (IH-2022) to optimize the regimen and improve survival outcomes.
Interventions
DRUGVDCLP+V
Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.
DRUG2VIP
Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.
Includes vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, dexamethasone, cytarabine, 6-mercaptopurine, and high-dose methotrexate.
DRUGMaintenance Therapy
Monthly MM regimen (6-mercaptopurine and methotrexate) and every 3 months VP (vincristine and prednisone) plus venetoclax.
DRUGBlinatumomab
Optional; 1 to 4 cycles (28 days each) based on patient choice, starting post-induction, alternating with chemotherapy cycles.
DRUGVenetoclax
Oral targeted therapy administered during induction, consolidation, and maintenance phases as per protocol
PROCEDURECNS Prophylaxis
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.
PROCEDURECAR-T Cell Therapy
Preconditioning regimen with fludarabine and cyclophosphamide (FC) administered after the third course (second consolidation) for patients receiving CAR-T.
PROCEDUREHematopoietic Stem Cell Transplantation (HSCT)
Allogeneic or autologous HSCT considered for high-risk patients or those with positive MRD after induction in CR1, provided a suitable donor is available.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed, previously untreated (except prednisone/hydroxyurea) Ph-negative ALL * Age ≥14 years, ≤60 years * ECOG performance status ≤2 * Adequate organ function (liver, kidney, cardiac) * For patients of childbearing potential: use of effective contraception * Willing and able to provide informed consent
Exclusion criteria
* Burkitt leukemia/lymphoma * Acute leukemia of ambiguous lineage * Pregnancy or lactation * Severe uncontrolled active infection * History of pancreatitis * Uncontrolled diabetes (HbA1c \>7.5%) * Active gastrointestinal bleeding within 6 months * Arterial/venous thrombosis within 6 months * Known HIV positivity * Severe psychiatric illness hindering compliance * Any other condition deemed unsuitable by the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-Free Survival | up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Complete Remission Rate | up to 1 year |
| MRD-negative CR rate by flow cytometry at 12 weeks | up to 12 weeks |
| MRD-negative CR rate by NGS at 12 weeks | up to 12 weeks |
| Overall Survival (OS) | Up to 5 years |
| Relapse-Free Survival (RFS) | Up to 5 years |
| Cumulative Incidence of Relapse | Up to 5 years |
Contacts
CONTACTHui Wei, Doctor
Outcome results
None listed