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

NCT05660473 | Recruiting Phase 2

• 1 other identifier: IIT2022052
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

Keywords

Philadelphia Chromosome-Negative; Acute Lymphoblastic Leukemia; Adolescent and Adult; Pediatric-inspired Regimen; Venetoclax

Outcome Measures

Primary Outcomes (1)

• MRD-negative complete remission rate measured by flow cytometry

  After induction (4 week)

Secondary Outcomes (5)

• Complete remission (CR) rate

  After 2 cycles of chemotherapy, an expected average of 3 months

• Overall survival (OS)

  Up to 5 years post-registration

• Relapse free survival (RFS)

  Up to 5 years post-registration

• Disease-free Survival (DFS)

  Up to 5 years post-registration

• The rate of adverse events

  An expected average of 24 months

Study Arms (1)

Pediatric-inspired Regimen Combined With Venetoclax

EXPERIMENTAL

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.

Drug: Vincristine; Drug: Daunorubicin; Drug: Cyclophosphamide; Drug: Pegaspargase; Drug: Prednisone; Drug: Cytarabine; Drug: 6-mercaptopurine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Venetoclax

Interventions

Vincristine DRUG

Anti-tumor alkaloids

Pediatric-inspired Regimen Combined With Venetoclax

Daunorubicin DRUG

Anthracycline

Pediatric-inspired Regimen Combined With Venetoclax

Cyclophosphamide DRUG

Alkylating agent

Pediatric-inspired Regimen Combined With Venetoclax

Pegaspargase DRUG

Polyethylene glycol (PEG) conjugated to L-asparaginase

Pediatric-inspired Regimen Combined With Venetoclax

Prednisone DRUG

Glucocorticoids

Pediatric-inspired Regimen Combined With Venetoclax

Cytarabine DRUG

Pyrimidine antimetabolites

Pediatric-inspired Regimen Combined With Venetoclax

6-mercaptopurine DRUG

Cell cycle-specific antitumor drug

Pediatric-inspired Regimen Combined With Venetoclax

Dexamethasone DRUG

Glucocorticoids

Pediatric-inspired Regimen Combined With Venetoclax

Methotrexate DRUG

Antifolate antineoplastic drug

Pediatric-inspired Regimen Combined With Venetoclax

Venetoclax DRUG

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

Pediatric-inspired Regimen Combined With Venetoclax

Eligibility Criteria

• Age: 14 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, 300020, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Vincristine; Daunorubicin; Cyclophosphamide; pegaspargase; Prednisone; Cytarabine; Mercaptopurine; Dexamethasone; Methotrexate; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Pregnadienetriols; Steroids, Fluorinated; Aminopterin; Pterins; Pteridines

Study Officials

• Jianxiang Wang, Dr

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxiang Wang, Dr

CONTACT

86-22-23909120; wangjx@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: August 1, 2022
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)