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 classificationAge: 14 -60 yearsMale or femaleECOG Performance Status 0-2Adequate 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 procedureExclusion Criteria:Burkitt lymphoma/leukemiaAcute Leukemia of Ambiguous LineageFemale patients who are pregnant or breast feedingUncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatmentHistory of pancreatitisPoorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excludedHistory of active gastrointestinal bleeding within the last 6 monthsHistory of arterial/venous thrombosis within the last 6 monthsKnown HIV seropositivityAny serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment