Efficacy and Safety of HVA Regimens as Salvage Treatment in rrAML

NCT04424147 | Completed Phase 2

• 1 other identifier: HVA in rrAML
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Acute Myeloid Leukemia; Relapsed Acute Erythroid Leukemia; Salvage Treatment; HVA Regimen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Safety and Tolerability of HVA treatment

  At the end of Cycle 2 (each cycle is 28 days)

• Disease-free survival

  one year

• Overall survival

  one year

Study Arms (1)

HVA treatment

EXPERIMENTAL

All patients with rrAML are treated with HVA regimen

Combination Product: HVA Regimens as Salvage Treatment

Interventions

HVA Regimens as Salvage Treatment COMBINATION_PRODUCT

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

HVA treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with rrAML Patients with the age of 18-65 years old

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Shenzhen Second People's Hospital: collaborator
• The Seventh Affiliated Hospital of Sun Yat-sen University: collaborator
• Maoming People's Hospital: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Shenzhen Hospital, Southern Medical University: collaborator
• Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• The First People's Hospital of Chenzhou: collaborator
• Peking University Shenzhen Hospital: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Related Publications (2)

• Yu S, Zhang Y, Yu G, Wang Y, Shao R, Du X, Xu N, Lin D, Zhao W, Zhang X, Xiao J, Sun Z, Deng L, Liang X, Zhang H, Guo Z, Dai M, Shi P, Huang F, Fan Z, Liu Q, Lin R, Jiang X, Xuan L, Liu Q, Jin H. Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study. J Intern Med. 2024 Feb;295(2):216-228. doi: 10.1111/joim.13738. Epub 2023 Oct 29.

  PMID: 37899297 DERIVED

• Jin H, Zhang Y, Yu S, Du X, Xu N, Shao R, Lin D, Chen Y, Xiao J, Sun Z, Deng L, Liang X, Zhang H, Guo Z, Dai M, Shi P, Huang F, Fan Z, Yin Z, Xuan L, Lin R, Jiang X, Yu G, Liu Q. Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial. J Hematol Oncol. 2023 Apr 29;16(1):42. doi: 10.1186/s13045-023-01437-1.

  PMID: 37120593 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Erythroblastic, Acute

Interventions

Salvage Therapy

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Qifa Liu

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients with rrAML are treated with HVA regimen

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 9, 2020
• Study Start: May 27, 2020
• Primary Completion: June 16, 2021
• Study Completion: June 30, 2022
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)