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

NCT ID: NCT05660473

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2027-12-30

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.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pediatric-inspired Regimen Combined With Venetoclax

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.

Group Type: EXPERIMENTAL

Vincristine

Intervention Type: DRUG

Anti-tumor alkaloids

Daunorubicin

Intervention Type: DRUG

Anthracycline

Cyclophosphamide

Intervention Type: DRUG

Alkylating agent

Pegaspargase

Intervention Type: DRUG

Polyethylene glycol (PEG) conjugated to L-asparaginase

Prednisone

Intervention Type: DRUG

Glucocorticoids

Cytarabine

Intervention Type: DRUG

Pyrimidine antimetabolites

6-mercaptopurine

Intervention Type: DRUG

Cell cycle-specific antitumor drug

Dexamethasone

Intervention Type: DRUG

Glucocorticoids

Methotrexate

Intervention Type: DRUG

Antifolate antineoplastic drug

Venetoclax

Intervention Type: DRUG

Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Interventions

Vincristine

Anti-tumor alkaloids

Intervention Type: DRUG

Daunorubicin

Anthracycline

Intervention Type: DRUG

Cyclophosphamide

Alkylating agent

Intervention Type: DRUG

Pegaspargase

Polyethylene glycol (PEG) conjugated to L-asparaginase

Intervention Type: DRUG

Prednisone

Glucocorticoids

Intervention Type: DRUG

Cytarabine

Pyrimidine antimetabolites

Intervention Type: DRUG

6-mercaptopurine

Cell cycle-specific antitumor drug

Intervention Type: DRUG

Dexamethasone

Glucocorticoids

Intervention Type: DRUG

Methotrexate

Antifolate antineoplastic drug

Intervention Type: DRUG

Venetoclax

Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Intervention Type: DRUG

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

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianxiang Wang, Dr

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Locations

Institute of Hematology & Blood Diseases Hospital

Tianjin, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianxiang Wang, Dr

Role: CONTACT

wangjx@ihcams.ac.cn

86-22-23909120

Facility Contacts

Jianxiang Wang, Dr.

Role: primary

wangjx@medmail.com.cn

86-22-23909120

Other Identifiers

IIT2022052

Identifier Type: -

Identifier Source: org_study_id