Low-dose Venetoclax and Azacitidine as Front-line Therapy in Newly Diagnosed AML

Phase 2

Completed

• Conditions: AML
• Interventions: Drug: Venetoclax 100 MG; Drug: Itraconazole capsule; Drug: Azacitidine Injection

• Registration Number: NCT05048615
• Lead Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Brief Summary

Venetoclax plus azacitidine are effective in treating newly diagnosed AML in patients who cannot recieve intensive chemotherapy. However there is no clinical data rewarding the efficacy and safety of low-dose venetoclax and azacitidine as first-line therapy.

Detailed Description

Venetoclax plus azacitidine are effective in treating newly diagnosed AML in patients who cannot recieve intensive chemotherapy. However there is no clinical data rewarding the efficacy and safety of low-dose venetoclax and azacitidine as first-line therapy. This phase 2 clinical trial will explore the efficacy and safety of low-dose venetoclax (100mg /day/21 days) and a fixed dose of azacitidine (75mg/m2, maximun dose 100mg, SC for seven consecutive days) for a maximun of two cycles.

Study Timeline

• Study Start: 2021-07-26
• Study First Submitted: 2021-07-26
• Study First Submitted QC: 2021-09-07
• Study First Posted: 2021-09-17
• Status Verified: 2023-01
• Primary Completion: 2023-01-20
• Study Completion: 2023-01-20
• Last Update Submitted: 2023-01-20
• Last Update Posted: 2023-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Age >18 years
2. Both genders
3. Diagnosis of non-m3 AML by the WHO 2016 diagnostic criteria
4. Patients eligible and not eligible for transplant
5. AML secondary to treatment or associated to myelodisplasia

Exclusion Criteria

1. AML with PML/RAR-alfa translocation t(15;17)
2. Central nervous system involvement
3. Poor functional status (ECOG>2)
4. Organic dysfunction (Marshall score ≥2)
5. Active infection
6. Use of other CYP3A4 inhibitors
7. Pregnancy
8. GFR <30 ml/min/1.72m2

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine	Azacitidine Injection	Patients will recieve Low-dose Venetoclax at a dose of 100mg/day por 21 days, oral itraconazol 100mg every 12 hours, and subcutaneous Azacitidine 75mg/m2 (maximun dose 100mg) daily for seven days. Each cycle duration is 21 days and patients will recieve a maximun of two cycles.
Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine	Itraconazole capsule	Patients will recieve Low-dose Venetoclax at a dose of 100mg/day por 21 days, oral itraconazol 100mg every 12 hours, and subcutaneous Azacitidine 75mg/m2 (maximun dose 100mg) daily for seven days. Each cycle duration is 21 days and patients will recieve a maximun of two cycles.
Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine	Venetoclax 100 MG	Patients will recieve Low-dose Venetoclax at a dose of 100mg/day por 21 days, oral itraconazol 100mg every 12 hours, and subcutaneous Azacitidine 75mg/m2 (maximun dose 100mg) daily for seven days. Each cycle duration is 21 days and patients will recieve a maximun of two cycles.

Primary Outcome Measures

Name	Time	Method
Feasibility will be address by obtaining the proportion of patients who need hospitalization	1 month	If therapy is feasible \>50% of patients will recieve their first cycle of treatment without hospitalization
Safety will be defined by the number of patients deceased before 14 days of initiating treatment	2 weeks	If therapy is safe then \<10% of patients will die in the first 14 days of treatment
Safety will be defined by the number of patients deceased before 30 days of initiating treatment	1 month	If therapy is safe then \<20% of patients will die in the first 30 days of treatment

Secondary Outcome Measures

Name	Time	Method
Efficacy will be achieved if the overall response rate is similar to standard of care (7+3)	2 months	If the therapy is effective then overall response rates will be similar to those reported with standard of care (7+3)

Trial Locations

Locations (1)

Andres Gomez; 🇲🇽 Monterrey, Nuevo LEON, Mexico