Study of Azacitidine Combined With Homoharringtonie Based Regimens in AML

September 2, 2022 updated by: Ge Zheng

Clinical Study of Azacitidine Combined With Homoharringtonie Based Regimens in Acute Myeloid Leukemia

Rencent years have witnessed great progress of the treatment of acute myeloid leukemia (AML). However, most patients have poor outcomes following the currently first-line DA(daunorubicin, cytarabine)/IA(Idarubicin, cytarabine) chemotherapy, espiecially for the older patients and those not eligiable for receiving allo-HSCT. Azacitidine (AZA)，a hypomethylating agent, targets epigenetic gene silencing by inhibiting gene expression against malignant phenotypes and is currently approved to treat AML based on the NCCN guidelines. The homoharringtonie (HHT) could induce AML cell lines and primary myeloid leukemia cell apoptosis, and the effect was dose dependent. While, HHT could also induce leukemia cells to differentiate into normal state, eventually achieve the goal of treatment, and control the disease. The investigators conducted a clinical study to evaluate the efficacy and safety of the AZA plus HAG(homoharringtonie, cytarabine, G-CSF), HIA(homoharringtonie, Idarubicin, cytarabine)/HDA(homoharringtonie, daunorubicin, cytarabine). This study is aimed to demonstrate the efficacy and safety advantages of the regimens that cotain homoharringtonie and azacitidine.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Currently, the treatment of acute myeloid leukemia (AML) still remains a therapeutic challenge. Patients received traditional chemotherapy have a low remission rate, poor prognosis and short survival for patients. New treatment strategies are needed in find out a better chemotherapy regimen.

Azacitidine (AZA), a hypomethylating agent, targets epigenetic gene silencing by inhibiting gene expression against malignant phenotypes. Azacitidine is currently approved to treat AML based on the NCCN guidelines. Novel combinations based on the azacitidine are currently undergoing, and the preliminary results brought promising hope to the treatment of AML.

The homoharringtonie (HHT) is a plant cytotoxic alkaloid derived from the trees of the genus Cephalotaxus. As a protein synthesis inhibitor, homoharringtonie plays a major role in the G1 / G2 phase in cells. In addition, it could induce AML cell lines and primary myeloid leukemia cell apoptosis, and the effect was dose dependent. Meanwhile it could also induce leukemia cells to differentiate into normal state, eventually controlled the progression of the disease.

Combination with azacitidine may become a new option.This study intends to apply azacitidine in combination with homoharringtonie for treating AML patients, aiming to improve the efficacy, reduce adverse events and improve the living qualities of patients.

Patients of de novo or relapsed AML(age≥60y or ineligibility to receive intensive chemotherapy) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), the AZA+HAG regimen was further given 4-6 cycles and followed by azacitidine maintenance or until the disease progresses.

Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HIA(homoharringtonie, Idarubicin, cytarabine) or AZA+HDA(homoharringtonie, daunorubicin, cytarabine) regiments as introduction therapy. After CR, post-remission therapy will follow with NCCN guidelines.

The investigators choose historical AML patients receiving tranditional chemotherapy as a control group, to evaluate the efficacy and safety profiles.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • NanJing, China, 210000
        • Recruiting
        • Department of Hematology, Zhongda Hospital, Medical School of Southeast University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnoised with acute myeloid leukemia
  2. Meet the criteria of the 2016 WHO classification system(APL were excluded), based on blood cell counting, bone marrow biopsy, and cytogeneic diagnosis
  3. Volunteered to sign the informed consent.

Exclusion Criteria:

  1. Mental disorders or other conditions that cannot meet the requirements of research, treatment and monitoring
  2. Uncontrolled cardiovascular disease
  3. Allergic to azacytarine, homoharringtonie, or other drugs of this study
  4. Any other conditions considered by the study investgators that are not suitable for participating in this clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Azacitidine plus HAG

Patients of de novo or relapsed AML(age≥60y or ineligibility to receive intensive chemotherapy) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), the AZA+HAG regimen was further given 4-6 cycles and followed by azacitidine maintenance or until the disease progresses.

AZA -Azacitidine HAG -Homoharringtonie, Cytarabine, G-CSF
Drug: Homoharringtonine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
  • HHT, Omacetaxine mepesuccinate
Drug: Azacitidine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
  • AZA
Experimental: Azacitidine plus HIA

Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HIA(homoharringtonie, Idarubicin, cytarabine) regiments as introduction therapy. After CR, post-remission therapy will follow with NCCN guidelines.

AZA -Azacitidine HIA -Homoharringtonie, Cytarabine, Idarubicin
Drug: Homoharringtonine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
  • HHT, Omacetaxine mepesuccinate
Drug: Azacitidine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
  • AZA
Experimental: Azacitidine plus HDA

Patients of de novo or relapsed AML(age<60y or eligible for intensive chemotherapy) will receive AZA +HDA(homoharringtonie, daunorubicin, cytarabine) regiments as introduction therapy., After CR, post-remission therapy will follow with NCCN guidelines.

AZA -Azacitidine HDA -Homoharringtonie, Cytarabine, Daunorubicin
Drug: Homoharringtonine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
  • HHT, Omacetaxine mepesuccinate
Drug: Azacitidine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
  • AZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CR
Time Frame: From date of randomization or initial treatment until the date of first documented disease relapse from any cause，assessed up to 100 weeks.
CR in months, in present of complete remission rate of all participants.
From date of randomization or initial treatment until the date of first documented disease relapse from any cause，assessed up to 100 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events rates
Time Frame: From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks.
Adverse events rates in percetage.
From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks.
RFS
Time Frame: From date of randomization or complete remission until the date of first documented disease relapse from any cause，assessed up to 100weeks.
RFS in months, in present of relapse free survival period of all participants
From date of randomization or complete remission until the date of first documented disease relapse from any cause，assessed up to 100weeks.
OS
Time Frame: From date of randomization until the date of first documented death from any cause or end of this study, whichever come first，assessed up to 100weeks.
OS in months, in present of overall survival period of all participants
From date of randomization until the date of first documented death from any cause or end of this study, whichever come first，assessed up to 100weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ge Zheng

Investigators

  • Study Director: Zheng Ge, M.D, Ph.D, Medical School of South East University, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Anticipated)

September 1, 2022

Study Completion (Anticipated)

December 30, 2022

Study Registration Dates

First Submitted

January 22, 2020

First Submitted That Met QC Criteria

January 28, 2020

First Posted (Actual)

January 30, 2020

Study Record Updates

Last Update Posted (Actual)

September 8, 2022

Last Update Submitted That Met QC Criteria

September 2, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZDYYGZ201912

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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