Study of VA Combined With HAAG Regimen in Newly Diagnosed Intermediate and High-risk AML Patients

A Single-center, Single-arm, Prospective Clinical Study on the Efficacy and Safety of Venetoclax and Azacitidine Combined With HAAG in the Induction Treatment of Intermediate and High-risk Acute Myeloid Leukemia

The purpose of this study is to evaluate the efficacy and safety of VA combined with HAAG in the induction treatment of newly diagnosed acute myeloid leukemia.

Study Overview

• Status: Recruiting
• Conditions: High Risk Acute Myeloid Leukemia; Intermediate Risk Acute Myeloid Leukemia
• Intervention / Treatment: Drug: venetoclax, azacitidine and HAAG regimen

Detailed Description

This is a single-center, single-arm, prospective clinical study in newly diagnosed intermediate and high-risk AML patients. The patients will receive venetoclax, azacitidine combined with HAAG regimen in the induction treatment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaowen Tang, Ph.D; Phone Number: (0086)51267780086; Email: xwtang1020@163.com
• Study Contact Backup: Name: Depei Wu, Ph.D; Phone Number: (0086)51267780086; Email: drwudepei@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • the First Affiliated Hospital of Soochow University
      • Contact: Xiaowen Tang, Ph.D; Phone Number: (0086)51267780086; Email: xwtang1020@163.com
      • Contact: Depei Wu, Ph.D; Phone Number: (0086)51267780086; Email: drwudepei@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Newly diagnosed intermediate and high-risk AML according to the WHO (2022) classification of acute myeloid leukemia (non-APL).
2. Age 18-65.
3. ECOG score: 0-2.
4. No history of previous chemotherapy or target therapy.
5. Serum total bilirubin <= 2 times the upper limit of normal (ULN), alanine aminotransferase (ALT) <= 1.5 times ULN, aspartate aminotransferase (AST) <=1.5 times ULN;
6. Creatinine clearance rate >=30 mL/min;
7. Serum lipase <= 1.5 times ULN, amylase <= 1.5 times ULN;
8. Capable to understand and willing to participate in this study, signed the informed consent form.

Exclusion Criteria:

1. AML transformed with chronic myelogenous leukemia.
2. Acute promyelocytic leukemia (type M3).
3. Patients with a second malignancy requiring treatment.
4. Patients with uncontrolled active infection.
5. Patients with left ventricular ejection fraction < 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification.
6. Patients with hepatic and renal inadequacy: total serum bilirubin >=2.0 mg/dl, AST >=3 times ULN, serum creatinine clearance (Ccr) <50 ml / min.
7. Patients with arterial oxygen saturation (SpO 2) was <95%.
8. Patients with HIV infection.
9. Patients with active hepatitis B or hepatitis C infection.
10. Patients with other commodities that the investigators considered not suitable for the enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VA combined with HAAG; This cohort will determine the safety and efficacy of venetoclax, azacitidine combined with HAAG regimen in newly diagnosed intermediate and high-risk AML patients.

Drug: venetoclax, azacitidine and HAAG regimen; Venetoclax:100mg, qd, d1;200mg, qd, d2;400 mg, qd, d3~10, per os; Azacitidine:75mg/m2/d, d1~7, subcutaneous injection; Homoharringtonine:1mg/d, d4~10, intravenous infusion; Aclarubicin:10mg/d, d4~7, intravenous infusion; Cytarabine:10mg/m2,q12h,d4~10, subcutaneous injection; Granulocyte colony-stimulating factor (G-CSF): 50-300μg/d (when WBC counts are less than 20×10^9/L ),subcutaneous injection;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete response rate (CRc; CR+CRi)	CRc includes complete response CR and CRi; CR was defined as < 5% bone marrow blasts in an aspirate with spicules, no blasts with Auer rods or persistence of extramedullary disease, and independent of transfusions; CRi: was defined as<5% bone marrow blasts, either ANC<1×10^9/L or platelets<100×10^9/L, transfusion independence but with persistence of cytopenia.	Day 28-35 of induction course

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	adverse events are evaluated with CTCAE V5.0.	2 years
Partial remission (PR)	PR was defined as decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate and the normalization of blood counts.	Day 28-35 of induction course
Relapse-free survival (RFS)	time from clinical CRc (CR and CRi) to the first relapse or death	3 years
Overall survival (OS)	time from the first day of treatment to death or lost to follow-up for any cause.	3 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Study Chair: Xiaowen Tang, Ph.D, the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: April 27, 2024
• First Submitted That Met QC Criteria: April 27, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 27, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: VA+HAAG

Drug and device information, study documents

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