Efficacy and Safety of HVA Regimens as Salvage Treatment in rrAML

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

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.

Study Overview

• Status: Completed
• Conditions: Refractory Acute Myeloid Leukemia; Relapsed Acute Erythroid Leukemia; Salvage Treatment; HVA Regimen
• Intervention / Treatment: Combination product: HVA Regimens as Salvage Treatment

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HVA treatment; All patients with rrAML are treated with HVA regimen	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Shenzhen Second People's Hospital; Peking University Shenzhen Hospital; The Seventh Affiliated Hospital of Sun Yat-sen University; Zhongshan People's Hospital, Guangdong, China; Maoming People's Hospital; Sun Yat-sen Memorial Hospital,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

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Actual): June 16, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 7, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Erythroblastic, Acute
• Other Study ID Numbers: HVA in rrAML

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No