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Venetoclax in Combination With 5 Days Azacitidine in Untreated AML Patients, Not Eligible for Standard Induction Therapy (VENAZA-5S)

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
VEN+AZA-5
Sponsored by
University of Leipzig
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Venclyxto, Venetoclax, Azacitidine, Hematologic Diseases, Acute Myelogenous Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Helios Klinikum Berlin-Buch Klinik für Hämatologie und StammzelltransplantationRecruiting
  • Klinikum Chemnitz gGmbH Klinik für lnnere Medizin Ill
  • Carl-Thiem-Klinikum Cottbus gGmbHRecruiting
  • Universitatsklinikum Carl Gustav Carus Dresden an der TU Dresden Medizinische Klinik und Poliklinik 1 Bereich Hamatologie
  • Universitätsklinikum Heidelberg, Innere Medizin V; Klinik für Hämatologie, Onkologie und Rheumatologie
  • Universitätsklinikum Leipzig, Klinik und Poliklinik für Hämatologie, Zelltherapie und HämostaseologieRecruiting
  • Kliniken Maria Hilf GmbH, Klinik für Hämatologie, Onkologie und Gastroenterologie
  • Rotkreuzklinikum München, III. Medizinische AbteilungRecruiting
  • Klinikum rechts der lsar der TU München, Klinik und Poliklinik für lnnere Medizin Ill
  • Kliniken Sindelfingen,Medizinische Klinik I

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VEN+AZA-5

Arm Description

Azacitidine (AZA) 75 mg/m2, d1-5 of each 28 day cycle (SC) in combination with Venetoclax (VEN): 400 mg daily (orally)

Outcomes

Primary Outcome Measures

The primary outcome measure is the response rate defined as the rate of CR/CRi after up to 6 cycles of therapy (best response).
Bone marrow assessments will be performed at least at screening, at the end of cycle 1, after cycle 4 and after cycle 6 resp. end of treatment (EOT). Criteria for disease status / response assessment follow the ELN-2022 recommendations .

Secondary Outcome Measures

Rate of CR or CRi by the Initiation of Cycle 2
Rate of CR or CRi by the Initiation of Cycle 2. Criteria for disease status / response assessment follow the European LeukemiaNet (ELN) - 2022 recommendations.
Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy
Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy. Criteria for disease status / response assessment follow the ELN-2022 recommendations.
Time from initiation of treatment (C1D1) until achievement of CR or CRi
Time from initiation of treatment (C1D1) until achievement of CR or CRi. Criteria for disease status / response assessment follow the ELN-2022 recommendations.
Objective response rate
Objective response rate (CR, CRh, CRi, MLFS). Criteria for disease status / response assessment follow the ELN-2022 recommendations.
Event free survival (EFS)
Event free survival (EFS), defined as the number of days from start of treatment to the date of relapse from CR or CRi, treatment failure (i.e., no CR or CRi after 6 cycles (each cycle is 28 days) of therapy or disease progression requiring treatment discontinuation), or death from any cause.
Overall survival (OS)
Overall survival (OS), defined as the number of days from start of treatment to death from any cause. After EOT, patients will be further followed up for survival until the end of the trial is reached (= last patient out, i.e. when the last surviving patient has reached the 3-month follow-up visit after EOT). Therefore, the duration of follow-up can differ between patients but is at least 3 months after EOT.
Descriptive assessment of measurable residual disease (MRD) levels on study treatment, determined by quantitative PCR or targeted next-generation sequencing
Determined by quantitative PCR or targeted next-generation sequencing. Molecular profiling and MRD assessment of all patients will be carried out centrally (Hämatologisches Diagnostiklabor, Universitätsklinikum Leipzig), at least at screening, at the end of cycle 1, after cycle 4 and after cycle 6 resp. end of treatment (EOT).
Time to treatment discontinuation
Time to treatment discontinuation, defined as the number of days from start of treatment to premature stop of treatment. The stop date is the date the first cycle that was not given should have started as scheduled. This endpoint will be analyzed with death and progression or relapse as competing risk.
Rate of patients with at least one treatment interruption
Rate of patients with at least one treatment interruption, i.e. a delay of the next cycle, and duration of treatment interruptions.
Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration
Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration
Duration of patient hospitalization
Duration of patient hospitalization, defined as days in hospital from start of treatment until EOT.
Quality of life (QoL)
The established cancer-specific Core Quality of Life questionnaire QLQ-C30 from the EORTC (European Organisation for Research) will be used for QoL measurement, at screening and at the beginning of each cycle and at EOT.

Full Information

First Posted
March 4, 2023
Last Updated
August 3, 2023
Sponsor
University of Leipzig
Collaborators
AbbVie, University Hospital Leipzig, Hematology Diagnostics Laboratory, University of Leipzig, Clinical Trial Centre (ZKS)
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1. Study Identification

Unique Protocol Identification Number
NCT05833438
Brief Title
Venetoclax in Combination With 5 Days Azacitidine in Untreated AML Patients, Not Eligible for Standard Induction Therapy
Acronym
VENAZA-5S
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 17, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Leipzig
Collaborators
AbbVie, University Hospital Leipzig, Hematology Diagnostics Laboratory, University of Leipzig, Clinical Trial Centre (ZKS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
Venclyxto, Venetoclax, Azacitidine, Hematologic Diseases, Acute Myelogenous Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VEN+AZA-5
Arm Type
Experimental
Arm Description
Azacitidine (AZA) 75 mg/m2, d1-5 of each 28 day cycle (SC) in combination with Venetoclax (VEN): 400 mg daily (orally)
Intervention Type
Drug
Intervention Name(s)
VEN+AZA-5
Intervention Description
Up to 6 cycles: Azacitidine (AZA) 75 mg/m2, d1-5 of each 28 day cycle (SC) in combination with Venetoclax (VEN): 400 mg daily (orally)
Primary Outcome Measure Information:
Title
The primary outcome measure is the response rate defined as the rate of CR/CRi after up to 6 cycles of therapy (best response).
Description
Bone marrow assessments will be performed at least at screening, at the end of cycle 1, after cycle 4 and after cycle 6 resp. end of treatment (EOT). Criteria for disease status / response assessment follow the ELN-2022 recommendations .
Time Frame
best response after up to 6 cycles (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Rate of CR or CRi by the Initiation of Cycle 2
Description
Rate of CR or CRi by the Initiation of Cycle 2. Criteria for disease status / response assessment follow the European LeukemiaNet (ELN) - 2022 recommendations.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy
Description
Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy. Criteria for disease status / response assessment follow the ELN-2022 recommendations.
Time Frame
after up to 6 cycles (each cycle is 28 days)
Title
Time from initiation of treatment (C1D1) until achievement of CR or CRi
Description
Time from initiation of treatment (C1D1) until achievement of CR or CRi. Criteria for disease status / response assessment follow the ELN-2022 recommendations.
Time Frame
from start of treatment (C1D1) until up to 6 cycles (each cycle is 28 days)
Title
Objective response rate
Description
Objective response rate (CR, CRh, CRi, MLFS). Criteria for disease status / response assessment follow the ELN-2022 recommendations.
Time Frame
at EOT, after up to 6 cycles therapy (each cycle is 28 days)
Title
Event free survival (EFS)
Description
Event free survival (EFS), defined as the number of days from start of treatment to the date of relapse from CR or CRi, treatment failure (i.e., no CR or CRi after 6 cycles (each cycle is 28 days) of therapy or disease progression requiring treatment discontinuation), or death from any cause.
Time Frame
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.
Title
Overall survival (OS)
Description
Overall survival (OS), defined as the number of days from start of treatment to death from any cause. After EOT, patients will be further followed up for survival until the end of the trial is reached (= last patient out, i.e. when the last surviving patient has reached the 3-month follow-up visit after EOT). Therefore, the duration of follow-up can differ between patients but is at least 3 months after EOT.
Time Frame
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.
Title
Descriptive assessment of measurable residual disease (MRD) levels on study treatment, determined by quantitative PCR or targeted next-generation sequencing
Description
Determined by quantitative PCR or targeted next-generation sequencing. Molecular profiling and MRD assessment of all patients will be carried out centrally (Hämatologisches Diagnostiklabor, Universitätsklinikum Leipzig), at least at screening, at the end of cycle 1, after cycle 4 and after cycle 6 resp. end of treatment (EOT).
Time Frame
From Screening until EOT (after up to 6 cycles (each cycle is 28 days))
Title
Time to treatment discontinuation
Description
Time to treatment discontinuation, defined as the number of days from start of treatment to premature stop of treatment. The stop date is the date the first cycle that was not given should have started as scheduled. This endpoint will be analyzed with death and progression or relapse as competing risk.
Time Frame
From start of treatment to day of treatment discontinuation (within up to 6 cycles (each cycle is 28 days))
Title
Rate of patients with at least one treatment interruption
Description
Rate of patients with at least one treatment interruption, i.e. a delay of the next cycle, and duration of treatment interruptions.
Time Frame
From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days))
Title
Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration
Description
Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration
Time Frame
From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days))
Title
Duration of patient hospitalization
Description
Duration of patient hospitalization, defined as days in hospital from start of treatment until EOT.
Time Frame
From start of treatment until EOT (after up to 6 cycles (each cycle is 28 days))
Title
Quality of life (QoL)
Description
The established cancer-specific Core Quality of Life questionnaire QLQ-C30 from the EORTC (European Organisation for Research) will be used for QoL measurement, at screening and at the beginning of each cycle and at EOT.
Time Frame
From Screening until EOT (after up to 6 cycles (each cycle is 28 days))
Other Pre-specified Outcome Measures:
Title
Incidence of Adverse Events [Safety and Tolerability]
Description
Descriptive analysis of adverse events for all patients having received at least one dose of investigational medicinal product (IMP). Adverse events will be documented from day 1 of the first treatment cycle until 35±7 days after EOT.
Time Frame
From start of treatment until 35±7 days after EOT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Klaus Metzeler, Prof. Dr.
Phone
+49 341 97-13050
Email
Klaus.Metzeler@medizin.uni-leipzig.de
First Name & Middle Initial & Last Name or Official Title & Degree
Uwe Platzbecker, Prof. Dr.
Phone
+49 341 97-13050
Email
uwe.platzbecker@medizin.uni-leipzig.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Klaus Metzeler, Prof. Dr.
Organizational Affiliation
Universitätsklinikum Leipzig, Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Helios Klinikum Berlin-Buch Klinik für Hämatologie und Stammzelltransplantation
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pearl van Heteren, Dr.
Email
Pearl.vanHeteren@helios-gesundheit.de
Facility Name
Klinikum Chemnitz gGmbH Klinik für lnnere Medizin Ill
City
Chemnitz
ZIP/Postal Code
09116
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Carl-Thiem-Klinikum Cottbus gGmbH
City
Cottbus
ZIP/Postal Code
03048
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Schmidt-Hieber, PD Dr.
Email
m.schmidt_hieber@ctk.de
Facility Name
Universitatsklinikum Carl Gustav Carus Dresden an der TU Dresden Medizinische Klinik und Poliklinik 1 Bereich Hamatologie
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Heidelberg, Innere Medizin V; Klinik für Hämatologie, Onkologie und Rheumatologie
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Leipzig, Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
City
Leipzig
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Klaus Metzeler, Prof. Dr.
Email
Klaus.Metzeler@medizin.uni-leipzig.de
Email
haematologie.studieneinheit@medizin.uni-leipzig.de
Facility Name
Kliniken Maria Hilf GmbH, Klinik für Hämatologie, Onkologie und Gastroenterologie
City
Mönchengladbach
ZIP/Postal Code
41063
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Rotkreuzklinikum München, III. Medizinische Abteilung
City
München
ZIP/Postal Code
80364
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Höllein, Prof.
Email
alexander.hoellein@swmbrk.de
Facility Name
Klinikum rechts der lsar der TU München, Klinik und Poliklinik für lnnere Medizin Ill
City
München
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Kliniken Sindelfingen,Medizinische Klinik I
City
Sindelfingen
ZIP/Postal Code
71065
Country
Germany
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in publications of this study, after deidentification
IPD Sharing Time Frame
Beginning 3 months and ending 3 years following article publication
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal for individual participant data meta-analysis.

Learn more about this trial

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

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