Clinical trial NCT04424147: Efficacy and Safety of HVA Regimens as Salvage Treatment in rrAML
Official title: Efficacy and Safety of HVA Regimens as Salvage Treatment in Relapsed/Refractory (rr) Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Acute Myeloid Leukemia
Relapsed Acute Erythroid Leukemia
Salvage Treatment
HVA Regimen
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Shenzhen Second People's Hospital
name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Maoming People's Hospital
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Shenzhen Hospital, Southern Medical University
name: Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
name: The First People's Hospital of Chenzhou
name: Peking University Shenzhen Hospital
name: Zhongshan People's Hospital, Guangdong, China
First posted: 2020-06-09
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with rrAML are treated with HVA regimen
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Complete response
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Safety and Tolerability of HVA treatment
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
measure: Disease-free survival
timeFrame: one year
measure: Overall survival
timeFrame: one year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Qifa Liu
role: PRINCIPAL_INVESTIGATOR
References: