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 (Verona)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04401748 |
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Recruitment Status :
Active, not recruiting
First Posted : May 26, 2020
Last Update Posted : December 8, 2022
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Myelodysplastic Syndrome (MDS) | Drug: Venetoclax Drug: Azacitidine Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 525 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 : | September 10, 2020 |
| Estimated Primary Completion Date : | February 14, 2025 |
| Estimated Study Completion Date : | February 14, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm 1: Venetoclax + Azacitidine (AZA)
Participants will receive venetoclax once daily (QD) (Days 1-14) in combination with AZA QD (7 days of the first 9 days) of each 28 day cycle.
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Drug: Venetoclax
Tablet: Oral
Other Names:
Drug: Azacitidine Subcutaneous (SC) or Intravenous (IV) injection
Other Name: AZA |
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Active Comparator: Arm 2: Placebo + Azacitidine
Participants will receive placebo once daily (QD) (Days 1-14) in combination with AZA QD (7 days of the first 9 days) of each 28 day cycle.
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Drug: Azacitidine
Subcutaneous (SC) or Intravenous (IV) injection
Other Name: AZA Drug: Placebo Tablet; Oral |
- 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).
- 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.
- 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 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, the initiation of post-treatment therapy, or death, whichever is earliest.
- 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".
- 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."
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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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.
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
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| Study Director: | ABBVIE INC. | AbbVie |
| 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: | December 8, 2022 |
| Last Verified: | December 2022 |
| 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, analyses plans, 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: | For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/ |
| 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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ |
| URL: | https://vivli.org/ourmember/abbvie/ |
| 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 |
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MDS Myelodysplastic Syndrome Venetoclax |
Azacitidine AZA Venclexta |
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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 |