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

Official title

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).

Overview

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

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.

Interventions

• 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.

Primary outcome measures

• ORR(overall response rate) [Time frame: 1 month]

Secondary outcome measures (3)

• OS (Overall survival) [Time frame: 2 years]
• EFS (Event-free survival) [Time frame: 2 years]
• Adverse events (AEs) [Time frame: 2 months]

Eligibility criteria

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;

• Age 18 to 59 years;
• Eastern Cooperative Oncology Group (ECOG) physical status score of 2 or 3;
• Expected survival time ≥3 months;
• 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;
• Not received radiotherapy, treatment regimens other than the VA regimen, or haematopoietic stem cell transplantation within 4 weeks prior to enrolment;
• Other comorbidities that, in the judgement of the physician, make the administration of intensive chemotherapy unsuitable;
• Ability to understand and willingness to sign the informed consent for this trial;
• The patient refuses intensive chemotherapy and has the willingness to accept non-intensive chemotherapy.

Exclusion criteria

• 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;
• Patients with FLT3 mutations and who were treated with targeted agents (inclusion is possible if the use of specific targeted agents is discontinued);
• Patients with less than 50% reduction of blasts after VA regimen;
• Patients with active CNS involvement;
• With prior treatment with chidamide;
• Clinically uncontrolled active infections (including bacterial, fungal or viral infections) and organ hemorrhage;
• Pregnant or lactating women;
• Participation in any other clinical trial within 3 months prior to VAC regimen;
• With other malignant tumours;
• With uncontrolled mental disorders;
• Any other condition that, in the opinion of the investigator, makes it inappropriate to participate in this trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Soochow University — Suzhou

Identifiers

NCT: NCT06220162 · SZAML04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗