Efficacy and Safety of HVA Regimens as Salvage Treatment in rrAML

Refractory Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04424147
• Other study ID #: HVA in rrAML
• Status: Completed
• Phase: Phase 2
• Start date: May 27, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: October 2022
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: June 30, 2022
• Est. primary completion date: June 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• HVA Regimen
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Refractory Acute Myeloid Leukemia
• Relapsed Acute Erythroid Leukemia
• Salvage Treatment

Intervention

Combination Product:
• HVA 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

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (10)

Lead Sponsor

Collaborator

Nanfang Hospital of Southern Medical University

Maoming People's Hospital, Peking University Shenzhen Hospital, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen Second People's Hospital, Sun Yat-sen Memorial Hospital,Sun Yat-sen University, The First People's Hospital of Chenzhou, The Seventh Affiliated Hospital of Sun Yat-sen University, Zhongshan City People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Disease-free survival		one year
Secondary	Overall survival		one year