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

Institute of Hematology & Blood Diseases Hospital, China

Status and phase

Enrolling

Phase 2

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Treatments

Drug: Daunorubicin

Drug: Cyclophosphamide

Drug: Cytarabine

Drug: Methotrexate

Drug: Dexamethasone

Drug: Vincristine

Drug: Pegaspargase

Drug: 6-mercaptopurine

Drug: Prednisone

Drug: Venetoclax

Study type

Interventional

Funder types

Other

Identifiers

NCT05660473

IIT2022052

Details and patient eligibility

About

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.

Enrollment

100 estimated patients

Sex

All

Ages

14 to 60 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

100 participants in 1 patient group

Pediatric-inspired Regimen Combined With Venetoclax

Experimental group

Description:

Induction therapy is administered as follows：Vincristine (VCR) 1.4 mg/m2 (maximum dose 2 mg) IV on D1,8,1,5,22; Daunorubicin (DNR) 30 mg/m2/day IV on D1-3; Cyclophosphamide (CTX) 1200 mg/m2 IV on D1,15; Pegaspargase 2500u/m2 IM on D5; Prednisone 1 mg/kg/d PO on D1-14, 0.5 mg/kg/d PO on D15-28; Venetoclax 100 mg PO on D6，200 mg on D7, 400mg on D8-14, All patients underwent bone marrow aspiration on day 14 during induction. Patients with bone marrow blasts ≥10% on day 14 of induction received 7 additional days of Venetoclax on day 15-22. Consolidation therapy is a combination of multi-drug pediatric-inspired regimen chemotherapy and Venetoclax. Maintenance therapy consisted of a monthly VMMP regimen (vincristine, mercaptopurine, methotrexate, prednisone) continuing until 3 years for male and 2.5 years for female patients.

Treatment: