Study of Azacitidine Combined With Homoharringtonie Based Regimens in AML

NCT04248595 | Unknown Phase 2 DMC

• 1 other identifier: ZDYYGZ201912
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute myeloid leukemia; Homoharringtonie; Azacitidine; Demethylation

Outcome Measures

Primary Outcomes (1)

• CR

  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 Outcomes (3)

• Adverse events rates

  From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks.

• RFS

  From date of randomization or complete remission until the date of first documented disease relapse from any cause，assessed up to 100weeks.

• OS

  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.

Study Arms (3)

Azacitidine plus HAG

EXPERIMENTAL

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; Drug: Azacitidine

Azacitidine plus HIA

EXPERIMENTAL

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; Drug: Azacitidine

Azacitidine plus HDA

EXPERIMENTAL

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; Drug: Azacitidine

Interventions

Homoharringtonine DRUG

De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.

Also known as: HHT, Omacetaxine mepesuccinate

Azacitidine plus HAG; Azacitidine plus HDA; Azacitidine plus HIA

Azacitidine DRUG

De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.

Also known as: AZA

Azacitidine plus HAG; Azacitidine plus HDA; Azacitidine plus HIA

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Ge Zheng: lead

Study Sites (1)

Department of Hematology, Zhongda Hospital, Medical School of Southeast University

Nanjing, 210000, China

RECRUITING

Related Publications (1)

• Li J, Huang Y, Hou Y, Gu Y, Song C, Ge Z. High efficacy of azacitidine combined with homoharringtonine, idarubicin, and cytarabine in newly diagnosed patients with AML: A single arm, phase 2 trial. Front Oncol. 2022 Dec 8;12:1069246. doi: 10.3389/fonc.2022.1069246. eCollection 2022.

  PMID: 36568250 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Homoharringtonine; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Zheng Ge, M.D, Ph.D

  Medical School of South East University, China

  STUDY DIRECTOR

Central Study Contacts

Zheng Ge, M.D, Ph.D

CONTACT

02583262468; Janege879@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Hematology

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 30, 2020
• Study Start: December 1, 2019
• Primary Completion: September 1, 2022
• Study Completion: December 30, 2022
• Last Updated: September 8, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)