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

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

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.

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