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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Ambulatory Low-dose Venetoclax and Azacitidne as First Line Therapy in Newly Diagnosed AML: a Pilot Study

Conditions
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AML

Intervention / Treatment
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* Drug: Venetoclax 100 MG
* Drug: Itraconazole capsule
* Drug: Azacitidine Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Both genders Diagnosis of non-m3 AML by the WHO 2016 diagnostic criteria Patients eligible and not eligible for transplant AML secondary to treatment or associated to myelodisplasia Exclusion Criteria: AML with PML/RAR-alfa translocation t(15;17) Central nervous system involvement Poor functional status (ECOG>2) Organic dysfunction (Marshall score ≥2) Active infection Use of other CYP3A4 inhibitors Pregnancy GFR <30 ml/min/1.72m2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A consecutive sample of 15 patients with newly diagnosed AML will be prospectively included in this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine<br>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. | Drug: Venetoclax 100 MG<br>* Patients will receive oral Venetoclax at a fixed dose of 100mg/day from day 1 to day 21 per cycle for a maximum of 2 cycles.<br>* Other names: Venclexta;Drug: Itraconazole capsule<br>* Patients will receive oral itraconazole at a dose of 100 mg every 12 hours from day 1 to day 21.<br>Drug: Azacitidine Injection<br>* Patients will receive a maximum of two cycles of daily subcutaneous Azacitidine at a dose of 75 mg/m2 (maximum 100 mg) from day 1 to day 7.<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy will be achieved if the overall response rate is similar to standard of care (7+3) | If the therapy is effective then overall response rates will be similar to those reported with standard of care (7+3) | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venetoclax, acute myeloid leukemia, azacitidine, first-line therapy, induction chemotherapy