HVA Regimen, Refractory Acute Myeloid Leukemia, Relapsed Acute Erythroid Leukemia, Salvage Treatment
Conditions
Brief summary
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.
Interventions
COMBINATION_PRODUCTHVA Regimens as Salvage Treatment
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
Sponsors
Shenzhen Second People's Hospital
The Seventh Affiliated Hospital of Sun Yat-sen University
Maoming People's Hospital
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Shenzhen Hospital, Southern Medical University
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
The First People's Hospital of Chenzhou
Peking University Shenzhen Hospital
Zhongshan People's Hospital, Guangdong, China
Nanfang Hospital, Southern Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients with rrAML are treated with HVA regimen
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response | At the end of Cycle 2 (each cycle is 28 days) | Blast rate lower than 5% with or without peripheral blood cell recover |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of HVA treatment | At the end of Cycle 2 (each cycle is 28 days) | The number of participants experiencing 3/4 degree bone marrow suppession and infection. |
| Disease-free survival | one year | — |
| Overall survival | one year | — |
Countries
China
Outcome results
None listed