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

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

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.

Study Overview

• Status: Completed
• Conditions: AML
• Intervention / Treatment: Drug: Venetoclax 100 MG; Drug: Itraconazole capsule; Drug: Azacitidine Injection

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andres Gomez; Phone Number: 818470002; Email: drgomezdeleon@gmail.com
• Study Contact Backup: Name: Perla Colunga; Phone Number: 818470002; Email: colunga.perla@gmail.com

Study Locations

• Mexico
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64710
      • Andres Gomez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine; 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; 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.; Other Names: Venclexta; Drug: Itraconazole capsule; Patients will receive oral itraconazole at a dose of 100 mg every 12 hours from day 1 to day 21.; Drug: 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.; Other Names: Vidaza

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez
• Investigators: Principal Investigator: David Gomez-Almaguer, Universidad Autonoma de Nuevo Leon

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): January 20, 2023
• Study Completion (Actual): January 20, 2023

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Estimate): January 24, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: venetoclax; acute myeloid leukemia; induction chemotherapy; azacitidine; first-line therapy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Venetoclax; Azacitidine; Itraconazole
• Other Study ID Numbers: HE21-00014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes