Clinical trial NCT05457361: VAH Versus VA for Salvage Therapy of R/R-AML
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Venetoclax Combined With Azacitidine Plus Homoharringtonine
Venetoclax Combined With Azacitidine
Keywords: Relapsed/refractory acute myeloid leukemia
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Zhongshan People's Hospital, Guangdong, China
name: Shenzhen Hospital of Southern Medical University
name: Peking University Shenzhen Hospital
name: Shenzhen Second People's Hospital
name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Southern Medical University, China
name: First People's Hospital of Chenzhou
name: The Affiliated Hospital of Qingdao University
name: First Affiliated Hospital of Guangxi Medical University
First posted: 2022-07-14
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Composite complete remission rate
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
measure: Overall survival
timeFrame: From date of randomization until date of death from any cause, assessed up to 12 months.
measure: Event-free survival
timeFrame: 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
measure: Relapse
timeFrame: 1 year
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Baseline to 30 day post the salvage therapy
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Department of Hematology,Nanfang Hospital, Southern Medical University
name: Qifa Liu
role: PRINCIPAL_INVESTIGATOR
References: