Venetoclax in Combination With 5 Days Azacitidine in Untreated AML Patients, Not Eligible for Standard Induction Therapy

A Single-arm, Pilot Study of Venetoclax in Combination With 5 Days Azacitidine in Treatment-naïve Subjects With Acute Myelogenous Leukemia Who Are ≥18 Years of Age and Not Eligible for Standard Induction Therapy (VENAZA-5S PILOT TRIAL)

Acute myeloid leukemia (AML): continuous oral Venetoclax (VEN) and 7 days of s.c. Azacitidine (AZA) per 28-day cycle = standard of care for intensive induction therapy ineligible AML patients in Germany

The VENAZA-5S pilot trial: AZA administration reduced to 5 days within each cycle to improve tolerability and treatment adherence due to less neutropenic infections, less treatment interruptions and less hospitalizations.

Acute myeloid leukemia (AML) is a uniformly fatal disease if untreated. The combination of continuous oral Venetoclax (VEN) and 7 days of s.c. Azacitidine (AZA) per 28-day cycle has recently emerged as the new standard of care for AML patient who are ineligible for intensive induction therapy, and has been widely adopted in Germany.

The VENAZA-5S pilot trial aims to reduce the reported hematological toxicity profile of this currently approved combination, while preserving efficacy, by modifying AZA administration to 5 days within each cycle. The hypothesis is that this modification will not interfere with the response rates achieved by the combination, but will rather improve tolerability and treatment adherence due to less neutropenic infections, less treatment interruptions and hospitalizations, and thus result in better quality of life and favorable long-term outcomes in elderly or comorbid AML patients. This single-arm pilot study is intended to generate first data on the efficacy and toxicity of 5 days AZA + VEN, which will be compared to a historical control cohort treated with the current standard of 7 days AZA + VEN.

Key Inclusion Criteria:

• Confirmed diagnosis of AML by World Health Organization (WHO) criteria 2016
• Ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age or comorbidities
• Age ≥ 18 years
• Life expectancy of at least 12 weeks

Key Exclusion Criteria:

• Prior treatment for AML or myelodysplastic syndrome (MDS) with one of the following:

  • Hypomethylating agent (HMA)
  • Chemotherapeutic agent
  • Chimeric Antigen Receptor (CAR)-T cell therapy
  • Experimental therapies
  • Note: Prior use of hydroxyurea is allowed

• History of myeloproliferative neoplasm (MPN)

• Diagnosis of acute promyelocytic leukemia (APL)

• Presence of favorable-risk karyotype abnormalities: t(15;17), t(8;21), inv(16) or t(16;16)