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

Venetoclax Combining Chidamide and Azacitidine (VCA) Regimen Followed by Dicitabine Combined With Liposome Mitoxantrone, Cytarabine, and G-CSF (D-MAG) Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) : A Multicenter, Prospective, Single Arm Clinical Trial

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)

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhifeng Li; Phone Number: +8613606901162; Email: lzf_xm@163.com
• Study Contact Backup: Name: Bing Xu, M.D.; Phone Number: +865922137255; Email: xubingzhangjian@126.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • Bing Xu
      • Contact: Bing Xu
      • Principal Investigator: Bing Xu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

  5) 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.

  4) 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.

  7) 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.

  8) 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.

  13) Any other circumstances that the investigator believes that the patient is not suitable 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: treatment arm; 2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once

Drug: Venetoclax Combining Chidamide and Azacitidine (VCA) regimen followed by dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen; venetoclax combining chidamide and azacitidine (VCA) 28 days per cycle × 2 cycles； 1) chidamide 30mg biw × 2weeks；2) venetoclax 200mg/d × 2 weeks 3) azacitidine 100mg/d d1-7 dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen 28 days per cycle ×2 cycles； 1）dicitabine 25mg d1-3，2）liposome mitoxantrone 20mg d4，3）cytarabine 10mg/m2 Q12h d1-7 4）G-CSF 300ug d-1 until WBC > 20×109/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rate	CR was <5% marrow blasts by morphology	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year leukemia free survival (LFS)	Leukemia-free survival (LFS) is defined as survival without evidence of relapse from treatment initiation	1 year from treatment initiation
1 year overall survival (OS)	Overall survival（OS）is defined as the time from treatment initiation to death from any cause.	1 year from treatment initiation
Adverse events	Adverse event is defined as any untoward medical occurrence associated with treatment	6 months
objective response rate (ORR)	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.	6 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Collaborators: Fujian Cancer Hospital; Huizhou Municipal Central Hospital; Chipscreen Biosciences, Ltd.; Fujian Provincial Hospital; Jieyang People's Hospital; Zhangzhou manicipal hospital of Fujian Province; CSPC Pharmaceutical Group Limited
• Investigators: Principal Investigator: Bing Xu, M.D., The First Affiliated Hospital of Xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 29, 2022
• First Submitted That Met QC Criteria: October 29, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: sequential treatment; newly diagnosed acute myeloid leukemia; liposome mitoxantrone
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Sensory System Agents; Antiviral Agents; Analgesics; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Venetoclax; Cytarabine; Azacitidine; Mitoxantrone
• Other Study ID Numbers: FXMH-AML-002; ChiCTR2200061925 (Registry Identifier: Chinese clinical trial registry)

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