VAH Versus VA for Salvage Therapy of R/R-AML

Venetoclax Combined With Azacitidine Plus Homoharringtonine Versus Venetoclax Combined With Azacitidine for Relapsed/Refractory Acute Myeloid Leukemia：an Open-label, Multicentre, Randomised Phase 3 Trial

This is a prospective, multi-center, phase 3 randomized controlled clinical study comparing VAH and VA regimens for the salvage treatment of the patients with relapsed/refractory AML. Approximately 164 subjects will be randomized in a 1:1 ratio to receive VAH regimen (82 subjects) or VA regimen (82 subjects) for salvage therapy. Randomization is done with permuted blocks (block size four), and implemented through an interactive web-based response system.

VAH regimen: VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.

VA regimen: The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.

The primary endpoint was overall response rate (ORR) after 2 cycles of trial therapy.

The secondary endpoints were CRc after 2 cycles of trial therapy, overall survival (OS), event-free survival (EFS) and relapse at 2 year, and safety.

Study Overview

• Status: Recruiting
• Conditions: Venetoclax Combined With Azacitidine Plus Homoharringtonine; Venetoclax Combined With Azacitidine
• Intervention / Treatment: Drug: VEN combined with azacitidine plus homoharringtonine; Drug: VEN combined with azacitidine

• Study Type: Interventional
• Enrollment (Anticipated): 162
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Qifa Liu; Phone Number: 86-20-61641612; Email: liuqifa628@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University
      • Contact: Qifa Liu; Phone Number: 86-20-61641612; Email: liuqifa628@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with relapsed/refractory AML The diagnosis of AML or relapsed AML was based on the criteria from NCCN, defined as recurrence of blasts in the peripheral blood (PB) or bone marrow (BM) blasts > 5% or development of extramedullary disease of patients after achieving a CR. Refractory AML was defined as no composite complete remission (CRc) and a reduction in bone marrow blasts of less than 50% after one cycle or no CRc after two cycles.
2. Age 18 to 65 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0-2
3. Sign informed consent form, have the ability to comply with study and follow-up procedures

Exclusion Criteria:

1. Acute promyelocytic leukemia (AML subtype M3)
2. Previous exposure to the treatment of VEN-based regimen
3. Life expectancy less than 30 days after salvage therapy
4. Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
5. Respiratory failure ( PaO2 ≤60mmHg)
6. Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal [ULN], alanine aminotransferase or aspartate aminotransferase ≥2 times the ULN)
7. Renal dysfunction (creatinine ≥2 times the ULN or creatinine clearance rate < 30 mL/min)
8. ECOG performance status 3, 4 or 5
9. With any conditions not suitable for the trial (investigators' decision)
10. Active acute or chronic graft-versus-host disease (GVHD). Active acute GVHD or chronic GVHD was defined as GVHD requiring either at least 1 mg/kg per day of prednisone (or equivalent) or treatment beyond systemic corticosteroids.
11. Patients with pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VAH regimen; VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.	Drug: VEN combined with azacitidine plus homoharringtonine; VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.
Active Comparator: VA regimen; The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.	Drug: VEN combined with azacitidine; The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Overall response including CR/CRi and PR	At the end of Cycle 2 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete remission rate	Composite complete remission including CR/CRi	At the end of Cycle 2 (each cycle is 28 days)
Overall survival	The time from enrolling to death or the last follow up	From date of randomization until date of death from any cause, assessed up to 12 months.
Event-free survival	The time from enrolling to no response, relapse, death or the last follow up	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Relapse	The event of relapse	1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Haematological toxicity and non-haematological toxicity	Baseline to 30 day post the salvage therapy

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: The Affiliated Hospital of Qingdao University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; First People's Hospital of Chenzhou; Shenzhen Second People's Hospital; Peking University Shenzhen Hospital; The Seventh Affiliated Hospital of Sun Yat-sen University; Southern Medical University, China; Zhongshan People's Hospital, Guangdong, China; First Affiliated Hospital of Guangxi Medical University; Shenzhen Hospital of Southern Medical University
• Investigators: Principal Investigator: Qifa Liu, Department of Hematology,Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: July 9, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 9, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Relapsed/refractory acute myeloid leukemia
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Protein Synthesis Inhibitors; Azacitidine; Homoharringtonine
• Other Study ID Numbers: VAH vs VA-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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