Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT04401748

Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome

Myelodysplastic Syndrome (MDS) is a group of disorders that gradually affect the ability of a person's bone marrow (semi-liquid tissue present in many bones like backbones) to produce normal blood cells. Some people with MDS have a risk of the disease progressing to acute myeloid leukemia (AML), and a risk of death from the disease itself. Symptoms of MDS include fatigue, shortness of breath, unusual paleness due to anemia (low red blood cell count), easy or unusual bruising, and red spots just beneath the skin caused by bleeding. The purpose of this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are when compared to AZA and a placebo (contains no medicine), in participants with newly diagnosed higher-risk MDS.

Venetoclax is an investigational drug being developed for the treatment of MDS. The study consists of two treatment arms - In one arm, participants will receive venetoclax and AZA. In another arm, participants will receive AZA and placebo. Adult participants with newly diagnosed higher-risk MDS will be enrolled. Around 500 participants will be enrolled in approximately 220 sites worldwide.

Participants in one arm will receive oral doses of venetoclax tablet and intravenous (infusion in the vein) or subcutaneous (given under the skin) AZA solution. Participants in another arm will receive oral doses of placebo tablet and intravenous or subcutaneous AZA solution.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Myelodysplastic Syndrome (MDS) Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Myelodysplastic Syndromes

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Duplicate_Blacktown Hospital /ID# 234079, Blacktown, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with a diagnosis of Myelodysplastic Syndrome (MDS) according to the 2016 World Health Organization (WHO) classification wtih presence of < 20% bone marrow blasts per marrow biopsy/aspirate at screening.
  • Participants must meet the following disease activity criteria:
  • Overall Revised International Prognostic Scoring System (IPSS-R) score > 3 (intermediate, high or very high).
  • Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
  • Hematopoietic stem cell transplant (HSCT) eligible with no pre-arranged HSCT at the time of Study Day 1, or HSCT ineligible without plan for HSCT at the time of Study Day 1.

Exclusion criteria

  • Prior therapy for MDS with any hypomethylating agent, chemotherapy, or allogenic stem cell transplantation.
  • Prior diagnosis of therapy-related MDS (t-MDS), MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.

Treatment and study plan

Venetoclax

Drug

Tablet: Oral

Other names: ABT-199, GDC-0199, Venclexta

Azacitidine

Drug

Subcutaneous (SC) or Intravenous (IV) injection

Other names: AZA

Placebo

Drug

Tablet; Oral

Primary outcomes

  1. Overall survival (OS)

    Time frame: Up To 5 Years

    OS is defined as the number of days from the date of randomization to the date of death of any cause, or last known date to be alive.

Secondary outcomes

  1. Modified Overall Response (mOR)

    Time frame: Up To 5 Years

    mOR [complete remission (CR) + marrow complete remission (mCR) + partial response (PR)] is defined as achieving a CR, mCR, or PR at any time point during the study per the modified International Working Group (IWG) 2006 criteria for myelodysplastic syndrome (MDS).

  2. Percentage of Participants Achieving Overall Hematological Improvement (HI)

    Time frame: Up to 5 Years

    Overall HI is defined as achieving the response of HI-platelet or HI-neutrophil, or HI-erythroid at any time point during the study prior to post-treatment therapy per the modified IWG 2006 criteria for MDS.

  3. Complete Remission (CR)

    Time frame: Up To 36 Months

    CR is defined as achieving a complete remission at any time point during the study per the modified International Working Group (IWG) 2006 criteria for myelodysplastic syndrome (MDS).

  4. Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent at Baseline

    Time frame: Up To 5 Years

    TI is when the participants who were transfusion dependent on red blood cell (RBC) and/or Platelet at baseline achieve transfusion independence post baseline. TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, or 1 day before the date of progressive disease/ relapse from CR or PR per the modified IWG 2006 criteria for MDS, or 1 day before the initiation of post-treatment therapy or 1 day before death, whichever is earliest.

  5. Time to Deterioration in Physical Functioning as Measured by Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scale

    Time frame: Up To 5 Years

    Time to deterioration in physical functioning, as measured by the EORTC QLQ-C30 physical functioning score is defined as the time from the date of randomization to the date of death of any cause, or the first time worsening of score from baseline >= a pre-specified threshold. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

  6. Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form (SF) 7a Scale Score

    Time frame: Up To 5 Years

    Fatigue will be assessed using the PROMIS Fatigue SF 7a Global Fatigue Score. PROMIS Fatigue SF 7a is a 7-item questionnaire that assesses the impact and experience of fatigue over the past 7 days. Participants rate items on a 5-point scale, with 1 as "never" an 5 as "always".

  7. Overall Response (OR)

    Time frame: Up To 5 Years

    OR [complete remission (CR) + partial response (PR)] is defined as achieving a CR or PR at any time point during the study per the modified IWG 2006 criteria for MDS.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • Genentech, Inc.

Registry information

Official study title

A Randomized, Double-Blind, Phase 3 Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Azacitidine in Patients Newly Diagnosed With Higher-Risk Myelodysplastic Syndrome (Higher-Risk MDS)

Acronym: Verona

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
May 26, 2020
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.