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Trial record 1 of 1 for:    M15-954
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Safety And Efficacy Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Complete Remission and Overall Survival In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome (Verona)

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ClinicalTrials.gov Identifier: NCT04401748
Recruitment Status : Recruiting
First Posted : May 26, 2020
Last Update Posted : September 10, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

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 200 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.


Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome (MDS) Drug: Venetoclax Drug: Azacitidine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : August 16, 2020
Estimated Primary Completion Date : February 14, 2025
Estimated Study Completion Date : February 14, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1: Venetoclax + Azacitidine (AZA)
Participants will receive venetoclax once daily (QD) (Days 1-14) in combination with AZA QD (Days 1-7) of each 28 day cycle.
Drug: Venetoclax
Tablet: Oral
Other Names:
  • ABT-199
  • GDC-0199

Drug: Azacitidine
Subcutaneous (SC) or Intravenous (IV) injection
Other Name: AZA

Active Comparator: Arm 2: Placebo + Azacitidine
Participants will receive placebo once daily (QD) (Days 1-14) in combination with AZA QD (Days 1-7) of each 28 day cycle.
Drug: Azacitidine
Subcutaneous (SC) or Intravenous (IV) injection
Other Name: AZA

Drug: Placebo
Tablet; Oral




Primary Outcome Measures :
  1. 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).

  2. 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 Outcome Measures :
  1. Percentage of Participants who Achieve Red Blood Cell (RBC) transfusion independence (TI) [ Time Frame: Up To 5 Years ]
    RBC TI is when the participants who were transfusion dependent at baseline achieve transfusion independence post baseline. RBC 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, the initiation of post-treatment therapy, or death, whichever is earliest.

  2. Percentage of Participants who Achieve Platelet Transfusion Independence (TI) [ Time Frame: Up To 5 Years ]
    Platelet TI is when participants who were transfusion dependent at baseline achieve transfusion independence post baseline. Platelet 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, the initiation of post-treatment therapy, or death, whichever is earliest.

  3. 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".

  4. Time to Deterioration in Physical Functioning as Measured by 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."

  5. 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.

  6. 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 IWG 2006 criteria for MDS.

  7. Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ) Physical Functioning Domain Score [ Time Frame: Up To 5 Years ]
    The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401748


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
Show Show 200 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
Additional Information:
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04401748    
Other Study ID Numbers: M15-954
2020-000744-55 ( EudraCT Number )
First Posted: May 26, 2020    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AbbVie:
MDS
Myelodysplastic Syndrome
Venetoclax
Azacitidine
AZA
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors