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

Conditions

AML

Keywords

acute myeloid leukemia, venetoclax, azacitidine, first-line therapy, induction chemotherapy

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.

Yadith Karina López‐García, Fernando De La Garza, Gerardo A De la Rosa-Flores, Edgar Ulises Coronado Alejandro, Antonio Vega‐Mateos et al. (11 authors)

Blood2023-11-023 citations

10.1182/blood-2023-188088

Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study

Fernando De la Garza‐Salazar, Perla R. Colunga‐Pedraza, David Gómez‐Almaguer, Valeria García-Zárate, Andrés Gómez‐De León

Leukemia Research2023-08-228 citations

10.1016/j.leukres.2023.107373

Interventions

DRUGVenetoclax 100 MG

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.

DRUGItraconazole capsule

Patients will receive oral itraconazole at a dose of 100 mg every 12 hours from day 1 to day 21.

DRUGAzacitidine Injection

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.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

This is an Open label study

Intervention model description

A consecutive sample of 15 patients with newly diagnosed AML will be prospectively included in this study.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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)

Countries

Mexico

Outcome results

None listed