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

AML Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05048615
• Other study ID #: HE21-00014
• Status: Completed
• Phase: Phase 2
• Start date: July 26, 2021
• Est. completion date: January 20, 2023

Study information

• Verified date: January 2023
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 20, 2023
• Est. primary completion date: January 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• AML

Intervention

Drug:
• Venetoclax 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.
• Itraconazole capsule
Patients will receive oral itraconazole at a dose of 100 mg every 12 hours from day 1 to day 21.
• Azacitidine 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.

Locations

Country	Name	City	State
Mexico	Andres Gomez	Monterrey	Nuevo LEON

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (4)

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. — View 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. — View 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. — View 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. Erratum In: Blood Adv. 2020 Mar 24;4(6):1020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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