Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

• Status: Recruiting
• Trial end date: 2027-12-30
• Target enrollment: 0
• Participant gender: All

Summary

The pediatric-inspired regimen has greatly improved the prognosis of adult patients with with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), but relapse remains a great challenge. Venetoclax (Ven) is an oral, selective inhibitor of B-cell lymphoma 2 (Bcl-2). Although this drug is currently used primarily for acute myeloid leukemia, in vitro as well as small cohort studies suggest a effect in acute lymphoblastic leukemia. This study proposes to combine pediatric-inspired regimen with venetoclax for the treatment of adult patients with Ph- ALL, aiming to improve the MRD-negative complete remission rate measured by flow cytometry after induction and to reduce relapse, thus further improving patients overall survival.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital
• Treatments: Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Mercaptopurine; Methotrexate; Pegaspargase; Prednisone; Venetoclax; Vincristine

Criteria

Inclusion Criteria:

• De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification

• Age: 14 -60 years

• Male or female

• ECOG Performance Status 0-2

• Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%;

• Subject has provided written informed consent prior to any screening procedure

Exclusion Criteria:

• Burkitt lymphoma/leukemia

• Acute Leukemia of Ambiguous Lineage

• Female patients who are pregnant or breast feeding

• Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment

• History of pancreatitis

• Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded

• History of active gastrointestinal bleeding within the last 6 months

• History of arterial/venous thrombosis within the last 6 months

• Known HIV seropositivity

• Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment