Clinical trial NCT04248595: Study of Azacitidine Combined With Homoharringtonie Based Regimens in AML
Official title: Clinical Study of Azacitidine Combined With Homoharringtonie Based Regimens in Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Acute myeloid leukemia
Homoharringtonie
Azacitidine
Demethylation
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2020-01-30
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: CR
timeFrame: 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:
measure: Adverse events rates
timeFrame: From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks.
measure: RFS
timeFrame: From date of randomization or complete remission until the date of first documented disease relapse from any cause，assessed up to 100weeks.
measure: OS
timeFrame: 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.
Other outcomes:
Locations:
city: NanJing
country: China
facility: Department of Hematology, Zhongda Hospital, Medical School of Southeast University
Study officials:
affiliation: Medical School of South East University, China
name: Zheng Ge, M.D, Ph.D
role: STUDY_DIRECTOR
References: