Study of Azacitidine Combined With Homoharringtonie Based Regimens in AML
Study Details
Study Description
Brief Summary
Rencent years have witnessed great progress of the treatment of acute myeloid leukemia. 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) was listed to methylation of drugs in China in 2018, is currently the only one approved methylation drugs in the treatment of AML(acute myeloid leukemia), in the NCCN guidelines. The homoharringtonie could induce AML(acute myeloid leukemia) 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 validate the efficacy and safety advantages of the regimens that cotain homoharringtonie and azacitidine, and to determine which regimen would receive more living benefits.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Currently, the treatment of acute myeloid leukemia still remains a therapeutic challenge. Patients received traditional chemotherapy have a low remission rate, poor prognosis and short survival period for patients. New treatment strategies are needed in find out a better chemotherapy regimen.
Azacitidine (AZA) was listed to methylation of drugs in China in 2018, is currently the only approved drug for use in acute myeloid leukemia to methylation of drugs, in the NCCN guidelines. New combinations based on the azacitidine are currently undergoing, and the preliminary results brought new hope to the treatment of AML.
The homoharringtonie was extracted from tricuspid plants of China. 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, reducing adverse reactions and improve the living qualities of patients.
Patients of denovo or relapsed AML(age≥60y) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), maintenance therapy with AZA+lenalidomide/AZA will be used every 4-6 weeks until progression or total of 12cycles.
Patients of denovo or relapsed AML(age<60y) 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 validate the efficacy and safety profiles.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Azacitidine plus HAG Patients of denovo or relapsed AML(age≥60y) will receive AZA+HAG (homoharringtonie, cytarabine, G-CSF) regiment as induction therapy. After complete remission(CR), maintenance therapy with AZA+lenalidomide/AZA will be used every 4-6 weeks until progression or total of 12cycles. 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:
Drug: Azacitidine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
|
| Experimental: Azacitidine plus HIA Patients of denovo or relapsed AML(age<60y) 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:
Drug: Azacitidine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
|
| Experimental: Azacitidine plus HDA Patients of denovo or relapsed AML(age<60y) will receive AZA +HDA(homoharringtonie, daunorubicin, cytarabine) regiments as introduction therapy., After CR, post-remission therapy will follow with NCCN guidelines. AZA -Azacitidine HIA -Homoharringtonie, Cytarabine, Daunorubicin |
Drug: Homoharringtonine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
Drug: Azacitidine
De novo AML or relapsed AML patients recieve chemotherapy regimen contained homoharringtonie and azacitidine.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- CR [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.
- PFS [From date of randomization or complete remission until the date of first documented disease progression from any cause，assessed up to 100weeks.]
PFS in months, in present of progression free survival period of all participants
- 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.]
OS in months, in present of over all survival period of all participants
Secondary Outcome Measures
- Adverse events rates [From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks.]
Adverse events rates in percetage.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hematology, Zhongda Hospital, Medical School of Southeast University | NanJing | China | 210000 |
Sponsors and Collaborators
- Ge Zheng
Investigators
- Study Director: Zheng Ge, M.D, Ph.D, Medical School of South East University, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZDYYGZ201912