Clinical trial NCT05048615: Low-dose Venetoclax and Azacitidine as Front-line Therapy in Newly Diagnosed AML
Official title: Efficacy and Safety of Ambulatory Low-dose Venetoclax and Azacitidne as First Line Therapy in Newly Diagnosed AML: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AML
Keywords: acute myeloid leukemia
venetoclax
azacitidine
first-line therapy
induction chemotherapy
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2021-09-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A consecutive sample of 15 patients with newly diagnosed AML will be prospectively included in this study.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility will be address by obtaining the proportion of patients who need hospitalization
timeFrame: 1 month
measure: Safety will be defined by the number of patients deceased before 14 days of initiating treatment
timeFrame: 2 weeks
measure: Safety will be defined by the number of patients deceased before 30 days of initiating treatment
timeFrame: 1 month
Secondary outcomes:
measure: Efficacy will be achieved if the overall response rate is similar to standard of care (7+3)
timeFrame: 2 months
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Andres Gomez
state: Nuevo LEON
Study officials:
affiliation: Universidad Autonoma de Nuevo Leon
name: David Gomez-Almaguer
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015 Sep 17;373(12):1136-52. doi: 10.1056/NEJMra1406184. No abstract available.
citation: Guerra VA, DiNardo C, Konopleva M. Venetoclax-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol. 2019 Jun;32(2):145-153. doi: 10.1016/j.beha.2019.05.008. Epub 2019 May 24.
citation: Pollyea DA, Amaya M, Strati P, Konopleva MY. Venetoclax for AML: changing the treatment paradigm. Blood Adv. 2019 Dec 23;3(24):4326-4335. doi: 10.1182/bloodadvances.2019000937.
citation: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.