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

Sponsor
Institute of Hematology & Blood Diseases Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05660473
Collaborator
(none)
100
1
1
60.5
1.7

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
Anticipated Study Start Date :
Dec 15, 2022
Anticipated Primary Completion Date :
Dec 15, 2024
Anticipated Study Completion Date :
Dec 30, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pediatric-inspired Regimen Combined With Venetoclax

Drug: Vincristine
Anti-tumor alkaloids

Drug: Daunorubicin
Anthracycline

Drug: Cyclophosphamide
Alkylating agent

Drug: Pegaspargase
Polyethylene glycol (PEG) conjugated to L-asparaginase

Drug: Prednisone
Glucocorticoids

Drug: Cytarabine
Pyrimidine antimetabolites

Drug: 6-mercaptopurine
Cell cycle-specific antitumor drug

Drug: Dexamethasone
Glucocorticoids

Drug: Methotrexate
Antifolate antineoplastic drug

Drug: Venetoclax
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Outcome Measures

Primary Outcome Measures

  1. MRD-negative complete remission rate measured by flow cytometry [After induction (4 week)]

Secondary Outcome Measures

  1. Complete remission (CR) rate [After 2 cycles of chemotherapy, an expected average of 3 months]

  2. Overall survival (OS) [Up to 5 years post-registration]

    From the date of registration to the date of death resulting from any cause

  3. Relapse free survival (RFS) [Up to 5 years post-registration]

    From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day

  4. Disease-free Survival (DFS) [Up to 5 years post-registration]

    From CR1 to relapse, death from any cause or last follow-up

  5. The rate of adverse events [An expected average of 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
14 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Institute of Hematology & Blood Diseases Hospital Tianjin China 300020

Sponsors and Collaborators

  • Institute of Hematology & Blood Diseases Hospital

Investigators

  • Principal Investigator: Jianxiang Wang, Dr, Institute of Hematology & Blood Diseases Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov Identifier:
NCT05660473
Other Study ID Numbers:
  • IIT2022052-EC-1
First Posted:
Dec 21, 2022
Last Update Posted:
Dec 21, 2022
Last Verified:
Dec 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Institute of Hematology & Blood Diseases Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 21, 2022