Efficacy and Safety of HVA Regimens as Salvage Treatment in rrAML

Study Overview
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Brief Summary
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Up Until now, there is not well acepted treatment for relapsed/refractory (rr) acute myeloid luekemia (AML), which has low complete response and poor survival. According to different guildlines, clinical trial is the first choice for the treatment of rrAML. High expression of BCL-2 and hypermethylation are very important factors for drug resistance in AML. Lots of studies have reported combination of BCL-2 inhibitor with hypomethylating agents (HMA) showed a promising efficacy in elder or unfit patients with newly diagnosed AML, however, presented not that exciting curing effect in rrAML. It is known that overexpression of MCL-1 and BCL-XL is the main reason for leukemia cells being resistant to BCL2 inhibitors. Since Homoharringtonine (HHT) could downregulate MCL-1 and BCL-XL in leukemia cells, there might be a synergic effect for combination of BCL-2 inhibitors with HHT, which has been proven in the treatment of lymphoma. Yet, there is not a report for the use of this combination in AML. In this single arm multi-centers prospective study, adult patients with rrAML are included and treated with BCL-2 inhibitor venetoclax at a dose of 400mg per day for 14 days, combined with azacitidine (AZA) at a dose of 75mg/m2 per day for 7 days, and HHT 1mg/m2 per day for 7 days, and then the eficacy and safety of HVA regimens as salvage treatment in rrAML are assessed.

Official Title
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Efficacy and Safety of HVA Regimens as Salvage Treatment in Relapsed/Refractory (rr) Acute Myeloid Leukemia (AML)

Conditions
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Refractory Acute Myeloid Leukemia, Relapsed Acute Erythroid Leukemia, Salvage Treatment, HVA Regimen

Intervention / Treatment
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* Combination Product: HVA Regimens as Salvage Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with rrAML Patients with the age of 18-65 years old Exclusion Criteria: Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Patients with any conditions not suitable for the trial (investigators' decision)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with rrAML are treated with HVA regimen
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HVA treatment<br>All patients with rrAML are treated with HVA regimen | Combination Product: HVA Regimens as Salvage Treatment<br>* venetoclax with a dose of 400mg per day for 14 days, combined with azacitidine (AZA) with a dose of 75mg/m2 per day for 7 days, and HHT 1mg/m2 per day for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | Blast rate lower than 5% with or without peripheral blood cell recover | At the end of Cycle 2 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of HVA treatment | The number of participants experiencing 3/4 degree bone marrow suppession and infection. | At the end of Cycle 2 (each cycle is 28 days) | 
| Disease-free survival |  | one year | 
| Overall survival |  | one year |