Pediatric-Inspired Regimen Combined With Venetoclax and Immunotherapy for Adult Ph-Negative Acute Lymphoblastic Leukemia

Institute of Hematology & Blood Diseases Hospital, China

Status: Enrolling

Conditions: Acute Lymphoblastic Leukemia, Adult

Treatments: Drug: Maintenance Therapy; Drug: 2VIP; Procedure: CAR-T Cell Therapy; Drug: VDCLP+V; Drug: Consolidation Therapy; Procedure: Hematopoietic Stem Cell Transplantation (HSCT); Procedure: CNS Prophylaxis; Drug: Blinatumomab; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT07495631

IIT2026003

Details and patient eligibility

About

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.

Full 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 to optimize the regimen and improve survival outcomes.

Enrollment: 43 estimated patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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43 participants in 2 patient groups

Chemotherapy induction Arm

Experimental group

Description:

Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax. Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen. Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate. Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles. CAR-T Cell Therapy- optional: the third cycle. Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months. CNS Prophylaxis Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.

Treatment:

Drug: Venetoclax

Procedure: Hematopoietic Stem Cell Transplantation (HSCT)

Procedure: CNS Prophylaxis

Drug: Blinatumomab

Drug: Consolidation Therapy

Drug: VDCLP+V

Procedure: CAR-T Cell Therapy

Drug: Maintenance Therapy

Immunotherapy induction Arm

Experimental group

Description:

Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone. For patients with CD22-positive B-ALL (≥20% blasts), especially those aged \>55 years, the 2VIP regimen is recommended. Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate. Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles. CAR-T Cell Therapy- optional: the third cycle. Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months. CNS Prophylaxis Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.

Treatment:

Drug: Venetoclax

Procedure: Hematopoietic Stem Cell Transplantation (HSCT)

Procedure: CNS Prophylaxis

Drug: Blinatumomab

Drug: Consolidation Therapy

Procedure: CAR-T Cell Therapy

Drug: Maintenance Therapy

Drug: 2VIP