VAC Regimen for AML Patients Who Failed to Response to VA Regimen

A Clinical Study of Chidamide in Combination With Venetoclax and Azacitidine (VAC) for Patients With Acute Myeloid Leukemia Who Did Not Achieve CR/CRi/MLFS (PR or NR) With One Cycle of Venetoclax and Azacitidine (VA).

Chidamide in combination with venetoclax and azacitidine (VAC) were expected to improve remission rate of patients following to VA regimen treatment failure.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: chidamide in combination with venetoclax and azacitidine (VAC)

Detailed Description

Venetoclax and azacitidine has become the standard first-line treatment for elderly/unsuitable AML patients who can't tolerate for intense chemotherapy.

However, a proportion of patients who were not able to achieve remission after failing to VA regimen and then were given the second cycle, and their rate of achieving remission was even lower. Chidamide down-regulates the expression of MCL and is expected to improve the remission rate further in combination with VA regimen.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sheng-Li Xue, M.D.; Phone Number: +8651267781139; Email: slxue@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Sheng-Li N Xue, M.D.; Phone Number: +8651267781139; Email: slxue@suda.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients with AML who are not suitable for intensive chemotherapy according to the WHO diagnosis: age ≥60 years or age <60 years but fulfil the following criteria;

1. Age 18 to 59 years;
2. Eastern Cooperative Oncology Group (ECOG) physical status score of 2 or 3;
3. Expected survival time ≥3 months;
4. Or fulfilment of severe cardiac, pulmonary, hepatic, or renal disease; (A) Presence of a cardiac history of congestive heart failure, or ejection fraction ≤ 50%, or presence of chronic stable angina; (B) Lung carbon monoxide diffusing capacity (DLCO) ≤ 65%, or first forced expiratory volume (FEV1) ≤ 65%; (C) Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 x upper limit of normal (ULN); (D) Creatinine clearance ≥ 30 mL/min to < 45 mL/min;
5. Not received radiotherapy, treatment regimens other than the VA regimen, or haematopoietic stem cell transplantation within 4 weeks prior to enrolment;
6. Other comorbidities that, in the judgement of the physician, make the administration of intensive chemotherapy unsuitable;
7. Ability to understand and willingness to sign the informed consent for this trial;
8. The patient refuses intensive chemotherapy and has the willingness to accept non-intensive chemotherapy.

Exclusion Criteria:

1. Patients with a history of myeloproliferative neoplasms (MPN), including myelofibrosis, thrombocythemia, polycythaemia vera, chronic granulocytic leukemia (CML) with or without BCR-ABL1 translocation, and AML or acute promyelocytic leukemia (APL) with BCR-ABL1 translocation;
2. Patients with FLT3 mutations and who were treated with targeted agents (inclusion is possible if the use of specific targeted agents is discontinued);
3. Patients with less than 50% reduction of blasts after VA regimen;
4. Patients with active CNS involvement;
5. With prior treatment with chidamide;
6. Clinically uncontrolled active infections (including bacterial, fungal or viral infections) and organ hemorrhage;
7. Pregnant or lactating women;
8. Participation in any other clinical trial within 3 months prior to VAC regimen;
9. With other malignant tumours;
10. With uncontrolled mental disorders;
11. Any other condition that, in the opinion of the investigator, makes it inappropriate to participate in this trial.

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: VAC regimen

Drug: chidamide in combination with venetoclax and azacitidine (VAC); Enrolled patients were given chidamide 10 mg every day on days 1-14, azacitidine 75mg/m2 every day on days 1-7, and oral venetoclax began at 100mg on day 1 and increased stepwise over 3 days to reach the target dose of 400mg (100mg, 200mg, and 400mg) on days 1-28. Dose adjustments for concomitant venetoclax with CYP3A4 inhibitors were made according to the literature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(overall response rate)	ORR was calculated as the sum of CR, CRi, MLFS and PR.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	It is evaluated and graded according to CTCAE 5.0.	2 months
OS (Overall survival)	OS was defined as the time from enrollment to this study to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	2 years
EFS (Event-free survival)	EFS was defined as the time from the initiation of CAV to treatment failure, relapse, death from any cause or the last follow-up.	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The Second People's Hospital of Huai'an; Jining Medical University; Affiliated Hospital of Nantong University; Northern Jiangsu People's Hospital; The First Affiliated Hospital of Bengbu Medical University
• Investigators: Study Chair: Sheng-Li Xue, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 6, 2024
• First Submitted That Met QC Criteria: January 21, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: AML venetoclax azacitidine chidamide unfit
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
• Other Study ID Numbers: SZAML04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No