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

NCT05048615 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: HE21-00014
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

AML

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Efficacy will be achieved if the overall response rate is similar to standard of care (7+3)

  2 months

Study Arms (1)

Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine

EXPERIMENTAL

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; Drug: Itraconazole capsule; Drug: Azacitidine Injection

Interventions

Venetoclax 100 MG DRUG

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.

Also known as: Venclexta

Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine

Itraconazole capsule DRUG

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

Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine

Azacitidine Injection DRUG

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.

Also known as: Vidaza

Low-dose Ventoclax and oral itraconazol plus subcutaneous Azacitdine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Universitario Dr. Jose E. Gonzalez: lead

Study Sites (1)

Andres Gomez

Monterrey, Nuevo León, 64710, Mexico

Location

Related Publications (5)

• 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.

  PMID: 26376137 BACKGROUND

• 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.

  PMID: 31203996 BACKGROUND

• 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.

  PMID: 31869416 BACKGROUND

• 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.

  PMID: 30361262 BACKGROUND

• De la Garza-Salazar F, Colunga-Pedraza PR, Gomez-Almaguer D, Garcia-Zarate VA, Gomez-De Leon A. Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. Leuk Res. 2023 Oct;133:107373. doi: 10.1016/j.leukres.2023.107373. Epub 2023 Aug 22.

  PMID: 37633156 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Itraconazole; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• David Gomez-Almaguer

  Universidad Autonoma de Nuevo Leon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This is an Open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hematology Service

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

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: September 17, 2021
• Study Start: July 26, 2021
• Primary Completion: January 20, 2023
• Study Completion: January 20, 2023
• Last Updated: January 25, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)