VCA Regimen Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Phase 2

Recruiting

• Conditions: Leukemia, Myeloid, Acute; AML Stage, Adult
• Interventions: Drug: Venetoclax Combining Chidamide and Azacitidine (VCA) regimen followed by dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen

• Registration Number: NCT05603884
• Lead Sponsor: The First Affiliated Hospital of Xiamen University

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Detailed Description

Elderly Patients with AML have inferior outcomes due to poor physical condition, and intolerant to conventional chemotherapy. The regimen of Venetoclax and Azacitidine has been widely used in these patients and has proved to achieve higher CR rate than low intensity therapy. However, the median duration of response (DOR) of this regimen is about one year. Chidamide is a histone deacetylase (HDAC) inhibitor and preclinical data showed adding low-dose Chidamide to venetoclax could significantly promoted apoptosis of leukemia cell lines. The Venetoclax Combining Chidamide and Azacitidine (VCA) regimen was applied to one 62-year-old male patient with AML who achieved CR. Meanwhile, Liposome mitoxantrone has better safety and tolerance than mitoxantrone in elderly patients. Thus, this study is intended to use 2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once to improve the median event free survival of elderly AML patients.

Study Timeline

• Study First Submitted: 2022-10-29
• Study First Submitted QC: 2022-10-29
• Study First Posted: 2022-11-03
• Study Start: 2022-12-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-19
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

• 1. Histologically confirmed acute myeloid leukemia (non-M3). Treatment-na?ve and unable to receive standard cytarabine and anthracycline induction regimens due to age or comorbidities or patient preference.

  2. Age ≥ 60 years old, male or female, with an expected survival more than 3 months.

  3. Estimated creatinine clearance ≥ 30 mL/min. 4) AST and ALT ≤ 3.0 x ULN (unless leukemic organ involvement). Bilirubin ≤ 1.5 x ULN (unless considered due to leukemic organ involvement).

  4. ECOG ≤ 2. 6) Able to understand and voluntarily provide informed consent.

Exclusion Criteria

• 1)Acute promyelocytic leukemia (APL) and low risk cytogenetics such as t(8;21), inv(16) or t(16;16).

  2. Active central nervous system leukemia. 3) History of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR- ABL1 translocation.

  3. HIV positive patients and/or HBV or HCV active infection (documented by HBV-DNA and HCV-RNA positive test) 5) Patients suffering from chronic respiratory diseases that require continuous oxygen inhalation, or a history of obvious renal, nervous system, psychiatric, endocrine, metabolic, immune, liver, and cardiovascular diseases 6) Patients suffering from malabsorption syndrome or other conditions that exclude enteral route of administration.

  4. Patients has clinically significant QTc prolongation (>450 ms in men; >470 ms in women), ventricular tachycardia and atrial fibrillation, second-degree heart block, myocardial infarction within the year prior to enrollment, and congestive heart failure;and patients with coronary heart disease with clinical symptoms requiring drug treatment.

  5. Active, uncontrolled severe infection. 9) History of other malignancies within 2 years, except for the following: Adequately treated cervix or breast cancer in situ; Basal cell cancer or local squamous cell carcinoma of the skin; 10) White blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis may meet this criterion.) 11) Mental disorders that hinder research participation 12) Participants have received the following treatments: hypomethylating agents, veneclax and/or chemotherapy for myelodysplastic syndrome (MDS), solid organ transplantation.

  6. Any other circumstances that the investigator believes that the patient is not suitable to participate in this trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment arm	Venetoclax Combining Chidamide and Azacitidine (VCA) regimen followed by dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen	2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once

Primary Outcome Measures

Name	Time	Method
Complete remission (CR) rate	6 months	CR was \<5% marrow blasts by morphology

Secondary Outcome Measures

Name	Time	Method
1 year leukemia free survival (LFS)	1 year from treatment initiation	Leukemia-free survival (LFS) is defined as survival without evidence of relapse from treatment initiation
1 year overall survival (OS)	1 year from treatment initiation	Overall survival（OS）is defined as the time from treatment initiation to death from any cause.
Adverse events	6 months	Adverse event is defined as any untoward medical occurrence associated with treatment
objective response rate (ORR)	6 months	ORR is defined as CR, CRi and PR. Partial remission (PR) is defined as a decrease of at least 50% in the percentage of blasts to 5 to 25% in the bone marrow aspirate and the normalization of blood counts.

Trial Locations

Locations (1)

Bing Xu; 🇨🇳 Xiamen, Fujian, China