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Individualized induction therapy will be applied to the non-elderly acute myeloid leukemia (AML) patients with adverse genetic risk features guided by rapid screening with fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), such as the combination of Venetoclax plus decitabine, and Sorafenib for patients with high (FMS)-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) allelic ratio. This study aims to improve induction therapy for non-elderly AML patients with adverse genetic risk features, reduce treatment-related complications, and improve overall survival.
The non-elderly AML patients who meet the adverse risk group defined as 2017 European LeukemiaNet (ELN) risk stratification, are more likely to be refractory to intensive induction and have low rates of long-term survival. Venetoclax (drug name) plus decitabine or azacitidine showed tolerable safety and favorable overall response rate (ORR )(complete remission (CR)+CR with incomplete hematologic recovery (CRi) rate: 67%) in elderly AML patients. In addition, combination therapy with sorafenib, cytarabine and idarubicin was able to induce a high CR rate in non-elderly AML patients with FLT3 mutations and a 1-year probability of survival of 74%. The fast next-generation sequencing together with FISH can identify the adverse genetic risk features in AML patients within 72 hours. Individualized induction therapy will be applied to the non-elderly AML patients with adverse genetic risk features guided by rapid screening with FISH and NGS, such as the combination of venetoclax plus decitabine, and Sorafenib for patients with high FLT3-ITD allelic ratio. This study aims to improve induction therapy for non-elderly AML patients with adverse genetic risk features, reduce treatment-related complications, and improve overall survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment regime | Experimental | combination of venetoclax plus azacitidine, and Sorafenib for patients with high FLT3-ITD allelic ratio |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| venetoclax combined with decitabine | Drug | combination of venetoclax plus decitabine, and sorafenib for patients with high FLT3-ITD allelic ratio. (On day 1 of cycle 1, decitabine 20 mg/m2 will be given intravenously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 28 day cycle is finished. For patients with high FLT3-ITD allelic ratio, sorafenib was administered at a dose of 400mg orally twice daily, on days 3 through 28. |
| Measure | Description | Time Frame |
|---|---|---|
| CR/CRi/morphologic leukemia free state (MLFS) | Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State(after one cycle or two cycles of induction therapy) | Study start date to study end date, or death, whichever comes first, up to 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Event Free Survival(EFS) | Event Free Survival | Study start date to study end date, or death, whichever comes first, up to 4 years |
| Overall Survival(OS) | Overall Survival |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| suning chen, professor | Contact | 8613814881746 | chensuning@sina.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology | Recruiting | Suzhou | Jiangsu | 215000 | China |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D000077157 | Sorafenib |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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|
|
| Study start date to study end date, or death, whichever comes first, up to 4 years |
| Incidence of Adverse Events | infection, blood transfusion, and other toxicity | Study start date to study end date, or death, whichever comes first, up to 4 years |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D010671 | Phenylurea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009536 | Niacinamide |
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D011725 | Pyridines |