Single Arm Study of Post-transplant Azacitidine and Chidamide for Prevention of Acute Myelogenous Leukemia Relapse

To Evaluate Safety and Efficiency of AZA Combined With Chidamide as Maintenance Therapy in High-risk Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation：A Multicenter, Single-arm Study

The goal of this clinical research study is to learn if azacitidine combined with Chidamide will help to control the disease in patients with high-risk AML after an allogeneic stem cell transplant. The safety of this combination will also be studied.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Azacitidine; Drug: Chidamide

Detailed Description

The Study Drug:

Azacitidine is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the "bad" genes, the tumor-fighting genes may be able to work better.

Chidamide exhibits potent inhibitory effect on cell viability of MDS and AML cells, and the possible mechanism may lie in the downregulation of JAK2/STAT3 signaling through SOCS3 upregulation.

Study Group： If you are found to be eligible to take part in this study,you will receive azacitidine and chidamide.

Study Drug Administration:

You will recieve six courses of azacitidine through a needle under your skin on Days 1-5.Each course is 28 days long.At the same time you will recieve oral chidamide per day for no more than 2 years.

The treatment will start after 60 days post-transplantation and your neutrophil count is of 1.5 × 10⁹ cells per L or higher and non-transfused platelets is of 80 × 10⁹ per L or higher.

The treatment would stop if neutrophil count is less than 0.5 × 10⁹ cells per L or platelets is less than 20 × 10⁹ per L.And it would also stop when grade 3/4 non-hematological adverse events happened.

Study Visit:

You may come back for study visits every month in a year when the treatment start.

Blood and urine will be drawn for routine tests every month. At 1,2,3,4,5,6,9 and 12 months,You will have a bone marrow aspiration to check the status of the disease.

You will have a electrocardiiogram test every 3 months to check the heart function.

Length of Study:

You will be on study treatment for up to 1 year.You will be taken off study early if you experience intolerable side effects or the disease gets worse.

End-of-Treatment Visit:

If you complete the planned treatment with azacitidine and chidamide, you will have an end-of-treatment visit:

Blood and urine will be drawn for routine tests. You will have a bone marrow aspiration to check the status of the disease. You will have a electrocardiiogram test every 3 months to check the heart function.

This is an investigational study. Azacitidine and chidamide are FDA approved and are commercially available for the treatment of acute leukemia.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rui Huang, Doctor; Phone Number: +8615918528317; Email: Rachelchn@163.com
• Study Contact Backup: Name: Yunqing Wang, Bachelor; Phone Number: +8618585509970; Email: Wangyun7q@163.com

Study Locations

• China
  • Guandong
    • Guanzhou, Guandong, China, 510250
      • Recruiting
      • Nanfang Hospital of Southern Medical University
      • Contact: Rui Huang, Doctor; Phone Number: +8615918528317; Email: Rachelchn@163.com
      • Contact: Yunqing Wang, Bachelor; Phone Number: +8618585509970; Email: Wangyun7q@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.Age 18 to 60 years old,both male and female
• 2.Be able to understand and sign informed consent
• 3.Patients with a diagnosis of AML not M3 according to the 2016 World Health Organization (WHO) Acute Myeloid Leukemia Classification and Diagnostic
• 4.Patients have AML with poor genetic abnormalities,primary refractory AML,relapsed AML or secondary AML
• 5.Patients with an ECOG performance status 0,1,2 or 3
• 6.Expected survival time ≥ 3 months
• 7.Non-hematological toxicity related to transplantation does not exceed Grade 2

• 8.Laboratory indicators meet the following standards:

  1. 7 days before the first day of the first course of treatment, bilirubin, ALT and AST were all less than 3 times the upper limit of normal.
  2. Measure twice within 7 days before the first day of the first course of treatment, at least 2 days apart, the neutrophil count are greater than 1.5×10/L and without G-CSF treatment.
  3. Measure twice within 7 days before the first day of the first course of treatment, at least 2 days apart, platelet count greater than 80×10/L and without platelet transfusion.
  4. Serum creatinine clearance rate is greater than 30ml/min.

Exclusion Criteria:

• 1.Uncontrollable active infection
• 2.Patients with active hepatitis B or C or HIV infection before enrollment
• 3.Have a grade III-IV graft-versus-host disease

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: Azacitidine combined with Chidamide; Patients will recieve six courses of azacitidine 100mg through a needle under your skin on Days 1-5.Each course is 28 days long.At the same time patients will recieve oral chidamide 5mg per day for no more than 2 years.	Drug: Azacitidine; Patients will recieve six courses of azacitidine 100mg through a needle under skin on Days 1-5.Each course is 28 days long.; Other Names: 5-AZC; Vidaza; 5-aza; 5-Azacitidine; Drug: Chidamide; Patients will recieve oral chidamide 5mg per day for no more than 2 years.; Other Names: Epidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Paticipants With Adverse Events as a Measure of Safety	Safety were measured with respect to: Safety measurements; Incidence of adverse events	From the day of stem cell transplantation to one year after stem cell transplantation
One year cumulative incidence of relapse	Leukemia relapse base on morphoogy criterion	From the day of stem cell transplantation to one year after stem cell transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapes-free Survival（RFS）	The time that a participant survives without relapes of the disease	From the day of stem cell transplantation to one year after stem cell transplantation
Overall survival（OS）	The time that a participant survives without death	From the day of stem cell transplantation to one year after stem cell transplantation
The cumulative Incidence rate of GVHD	acute GVHD and chronic GVHD diagnosis based on MIH criterion	From the day of stem cell transplantation to one year after stem cell transplantation

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Investigators: Principal Investigator: Rui Huang, Doctor, Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: March 6, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Azacitidine; Acute myelogenous leukemia; Maintenance therapy; Chidamide; Allogenetic stem cell transplant; High-risk AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: AZA+Chidamide

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share our data within 6 months after the end of the trial. You can ask us for data or obtain it on the Clinical Trial Management Public Platform of clinical trial.
• IPD Sharing Time Frame: The data will be available and permanently disclosed within 6 months after the trial.
• IPD Sharing Access Criteria: You can log in to the website for data access or contact us for data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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