Clinical trial NCT05833438: Venetoclax in Combination with 5 Days Azacitidine in Untreated AML Patients, Not Eligible for Standard Induction Therapy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Venclyxto
Venetoclax
Azacitidine
Hematologic Diseases
Acute Myelogenous Leukemia
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: AbbVie
name: University Hospital Leipzig, Hematology Diagnostics Laboratory
name: University of Leipzig, Clinical Trial Centre (ZKS)
First posted: 2023-04-27
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: The primary outcome measure is the response rate defined as the rate of CR/CRi after up to 6 cycles of therapy (best response).
timeFrame: best response after up to 6 cycles (each cycle is 28 days)
Secondary outcomes:
measure: Rate of CR or CRi by the Initiation of Cycle 2
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy
timeFrame: after up to 6 cycles (each cycle is 28 days)
measure: Time from initiation of treatment (C1D1) until achievement of CR or CRi
timeFrame: from start of treatment (C1D1) until up to 6 cycles (each cycle is 28 days)
measure: Objective response rate
timeFrame: at EOT, after up to 6 cycles therapy (each cycle is 28 days)
measure: Event free survival (EFS)
timeFrame: From start of treatment to the date of relapse from CR or CRi, treatment failure (i.e., no CR or CRi after up to 6 cycles (each cycle is 28 days) of therapy or disease progression requiring treatment discontinuation), or death from any cause.
measure: Overall survival (OS)
timeFrame: From start of treatment to date of death from any cause. OS will be assessed until 3 months after end of treatment of the last patient on study.
measure: Descriptive assessment of measurable residual disease (MRD) levels on study treatment, determined by quantitative PCR or targeted next-generation sequencing
timeFrame: From Screening until EOT (after up to 6 cycles (each cycle is 28 days))
measure: Time to treatment discontinuation
timeFrame: From start of treatment to day of treatment discontinuation (within up to 6 cycles (each cycle is 28 days))
measure: Rate of patients with at least one treatment interruption
timeFrame: From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days))
measure: Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration
timeFrame: From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days))
measure: Duration of patient hospitalization
timeFrame: From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days))
measure: Quality of life (QoL)
timeFrame: From Screening until EOT (after up to 6 cycles (each cycle is 28 days))
Other outcomes:
measure: Incidence of Adverse Events [Safety and Tolerability]
timeFrame: From start of treatment until 35±7 days after EOT
Locations:
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch Klinik für Hämatologie und Stammzelltransplantation
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH Klinik für lnnere Medizin Ill
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus gGmbH
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus Dresden an der TU Dresden Medizinische Klinik und Poliklinik 1 Bereich Hamatologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Innere Medizin V; Klinik für Hämatologie, Onkologie und Rheumatologie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH, Klinik für Hämatologie, Onkologie und Gastroenterologie
city: München
country: Germany
facility: Rotkreuzklinikum München, III. Medizinische Abteilung
city: München
country: Germany
facility: Klinikum rechts der lsar der TU München, Klinik und Poliklinik für lnnere Medizin Ill
city: Sindelfingen
country: Germany
facility: Kliniken Sindelfingen,Medizinische Klinik I
Study officials:
affiliation: Universitätsklinikum Leipzig, Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
name: Klaus Metzeler, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: