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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

NCT04401748

Description:

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: M15-954
  • SECONDARY ID: 2020-000744-55
  • NCT ID: NCT04401748

Conditions

  • Myelodysplastic Syndrome (MDS)

Interventions

DrugSynonymsArms
VenetoclaxABT-199, GDC-0199Arm 1: Venetoclax + Azacitidine (AZA)
AzacitidineAZAArm 1: Venetoclax + Azacitidine (AZA)
PlaceboArm 2: Placebo + Azacitidine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Venetoclax + Azacitidine (AZA)ExperimentalParticipants will receive venetoclax once daily (QD) (Days 1-14) in combination with AZA QD (Days 1-7) of each 28 day cycle.
  • Venetoclax
  • Azacitidine
Arm 2: Placebo + AzacitidineActive ComparatorParticipants will receive placebo once daily (QD) (Days 1-14) in combination with AZA QD (Days 1-7) of each 28 day cycle.
  • Azacitidine
  • Placebo

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission (CR)
Time Frame:Up To 36 Months
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Modified Overall Response (mOR)
Time Frame:Up To 5 Years
Safety Issue:
Description: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.
Measure:Percentage of Participants who Achieve Red Blood Cell (RBC) transfusion independence (TI)
Time Frame:Up To 5 Years
Safety Issue:
Description: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.
Measure:Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form (SF) 7a Scale Score.
Time Frame:Up To 5 Years
Safety Issue:
Description: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".
Measure: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
Safety Issue:
Description: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."
Measure:Percentage of Participants who Achieve Platelet Transfusion Independence (TI)
Time Frame:Up To 5 Years
Safety Issue:
Description: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.
Measure:Overall Response (OR)
Time Frame:Up To 5 Years
Safety Issue:
Description: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.
Measure:Time to Deterioration in Physical Functioning as Measured by EORTC QLQ-C30 Scale
Time Frame:Up To 5 Years
Safety Issue:
Description: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."

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • MDS
  • Myelodysplastic Syndrome
  • Venetoclax
  • Azacitidine
  • AZA

Last Updated

May 22, 2020