Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in Newly Diagnosed ETP-ALL

A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in the Treatment of Adult Newly Diagnosed Early Precursor T-cell Acute Lymphoblastic Leukemia (ETP-ALL)

ETP-ALL is a subtype of T-cell acute lymphoblastic leukemia (T-ALL) with poor outcomes and prognosis. Effective induction therapy is crucial in improving the treatment effect. Based on our laboratory research and clinical practice, the venetoclax plus HAG regimen shows promising efficacy in treating ETP-ALL. Therefore, we plan to conduct a prospective, multicenter Phase III clinical study to evaluate the efficacy of the venetoclax plus HAG regimen in treating newly diagnosed ETP-ALL patients.

Study Overview

• Status: Recruiting
• Conditions: ETP-ALL
• Intervention / Treatment: Drug: Daunorubicin; Drug: Homoharringtonine; Drug: venetoclax; Drug: Cytarabine; Drug: G-CSF; Drug: Vindesine; Drug: cyclophosphamide; Drug: Dexamethasone; Drug: L-ASP

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Jie Jin, PhD&MD; Phone Number: 13705716779; Email: jiej0503@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥14 and <75 years old.
• Diagnosed with ETP-ALL (including near-ETP ALL) before enrollment.
• Newly diagnosed patients.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Expected survival of ≥3 months.
• Able to undergo oral treatment with venetoclax.
• No organ dysfunction that would restrict the treatment administered
• Understanding of the study and signing of the informed consent form.
• Men, women of childbearing potential (postmenopausal women must have been amenorrheic for at least 12 months to be considered infertile), and their partners must voluntarily use effective contraception methods as deemed appropriate by the investigator during the treatment period and for at least 12 months after the last dose of the study drug.

Exclusion Criteria:

• Patients who are unable to take venetoclax by mouth;
• Patients with severe heart, lung, liver, kidney, or other organ dysfunction that may restrict their participation in this trial due to diseases;
• Evidence of other clinically significant uncontrolled condition(s) such as uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• A history of other malignant tumors within the past 5 years, excluding localized thyroid cancer and in situ skin cancer;
• Serum total bilirubin >1.5 ULN (upper limit of normal) (excluding leukemia infiltration); ALT or AST or ALP >5 ULN; serum creatinine >1.5 ULN and creatinine clearance rate <40 mL/min; LVEF <50%;
• Known HIV infection;
• Known central nervous system leukemia infiltration;
• Gastrointestinal diseases known to affect venetoclax absorption as judged by the investigator;
• Inability to understand or comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VHAG group; Venetoclax: 100mg on day 1, 200mg on day 2, and 400mg on days 3-14, if the blast cells in bone marrow were more than 5% on day 14, the patient continued to receive venetoclax 400mg until day 28. HHT:1.4 mg/m2,2mg maximum daily, intravenously daily from on d1-7 Cytarabine :10 mg/m2 subcutaneously every 12h on d1-14（d10-d14） G-CSF: 100ug/m2 daily on d1-14 if WBC count <10*10E9/L	Drug: Homoharringtonine; Intravenous infusion; Drug: venetoclax; Orally by mouth; Drug: Cytarabine; subcutaneous injection or Intravenous infusion; Drug: G-CSF; subcutaneous injection
Active Comparator: Traditional Chemotherapy Regimen group; VDCLP regimen; VD(/I) CP regimen; Hyper CVAD-A regimen; VDLP regimen	Drug: Daunorubicin; Intravenous infusion; Drug: Cytarabine; subcutaneous injection or Intravenous infusion; Drug: Vindesine; Intravenous infusion; Drug: cyclophosphamide; Intravenous infusion; Drug: Dexamethasone; Intravenous infusion or orally; Drug: L-ASP; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year EFS	1-year event free survival rate	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR/CRi	Complete remission/complete remission with incomplete count recovery	At the end of Cycle 1 (up to 42 days)
OS	Overall survival	through study completion, up to 3 years
MRD	Percentage of participants who converted to MRD < 10^-3 after the first cycle of treatment.	At the end of Cycle 1 (up to 42 days)
Safety of induction therapy	Adverse events	At the end of Cycle 1 (up to 42 days)

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: April 1, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Synthesis Inhibitors; Antibiotics, Antineoplastic; Dexamethasone; Cyclophosphamide; Venetoclax; Cytarabine; Daunorubicin; Vindesine; Homoharringtonine
• Other Study ID Numbers: 20240030C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No