Clinical trial NCT05660473: Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
Official title: Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Keywords: Philadelphia Chromosome-Negative
Acute Lymphoblastic Leukemia
Adolescent and Adult
Pediatric-inspired Regimen
Venetoclax
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2022-12-21
Enrollment: 100
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: MRD-negative complete remission rate measured by flow cytometry
timeFrame: After induction (4 week)
Secondary outcomes:
measure: Complete remission (CR) rate
timeFrame: After 2 cycles of chemotherapy, an expected average of 3 months
measure: Overall survival (OS)
timeFrame: Up to 5 years post-registration
measure: Relapse free survival (RFS)
timeFrame: Up to 5 years post-registration
measure: Disease-free Survival (DFS)
timeFrame: Up to 5 years post-registration
measure: The rate of adverse events
timeFrame: An expected average of 24 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Jianxiang Wang, Dr
role: PRINCIPAL_INVESTIGATOR
References: