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A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)

NCT04161885

Description:

The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Relapse Free Survival (RFS) in AML patients compared to Best Supportive Care (BSC) when given as maintenance therapy following allogeneic stem cell transplantation (SCT). This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who are greater than or equal to 18 years old; Part 2 (Randomization) which may include participants who are greater than or equal to 12 years old. During Part 1, recommended Phase 3 dose of venetoclax in combination with azacitidine will be determined and during Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with BSC (Part 2 Arm B).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)
  • Official Title: A Randomized, Open Label Phase 3 Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine After Allogeneic Stem Cell Transplantation in Subjects With Acute Myeloid Leukemia (AML) (VIALE-T)

Clinical Trial IDs

  • ORG STUDY ID: M19-063
  • SECONDARY ID: 2019-002621-30
  • NCT ID: NCT04161885

Conditions

  • Acute Myeloid Leukemia (AML)
  • Cancer

Interventions

DrugSynonymsArms
VenetoclaxABT-199, GDC-0199, VENCLEXTAPart 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care
AzacitidinePart 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care

Purpose

The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Relapse Free Survival (RFS) in AML patients compared to Best Supportive Care (BSC) when given as maintenance therapy following allogeneic stem cell transplantation (SCT). This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who are greater than or equal to 18 years old; Part 2 (Randomization) which may include participants who are greater than or equal to 12 years old. During Part 1, recommended Phase 3 dose of venetoclax in combination with azacitidine will be determined and during Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with BSC (Part 2 Arm B).

Trial Arms

NameTypeDescriptionInterventions
Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive CareExperimentalParticipants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)
  • Venetoclax
  • Azacitidine
Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSCExperimentalParticipants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).
  • Venetoclax
  • Azacitidine
Part 2: Arm B - Best Supportive Care (BSC)ExperimentalParticipants will receive treatment as prescribed by their physician according to the BSC for up to 24 cycles (1 cycle = 28 days)

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Participants must be at least 18 years old for Part 1 and, at least 12 years old for
                 Part 2.
    
              -  Participant must be diagnosed with AML by World Health Organization (WHO) criteria
                 (2017) and either be planning for allogeneic stem cell transplantation or have
                 received allogeneic stem cell transplantation within the past 14 days.
    
              -  Blast percentage in bone marrow before transplant must be < 10%.
    
              -  Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must
                 be < 5% after transplant.
    
              -  Participant meet adequate renal, hepatic and hematologic criteria as described in the
                 protocol.
    
              -  Participants >= 17 years old must have a Karnofsky Performance Scale (KPS) score > 50
                 and participants between 12 to 16 years old must have a Lansky Play Performance Scale
                 score > 40.
    
            Exclusion Criteria:
    
              -  History of disease progression during prior treatment with venetoclax.
    
              -  History of any other malignancy within 2 years prior to study entry, except for:
                 Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of
                 breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the
                 skin; previous malignancy confined and surgically resected (or treated with other
                 modalities) with curative intent; Myelodysplastic Syndrome.
    
              -  Participant has known infection with HIV or history of being positive for hepatitis B
                 virus (HBV) or hepatitis C virus (HCV) infection.
    
              -  Presence of clinical or laboratory symptoms/signs of extramedullary myeloid
                 malignancy.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:12 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)
    Time Frame:Upto the first treatment cycle (28 days)
    Safety Issue:
    Description:DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax and AZA as described in the protocol and evaluated by the Investigator and the sponsor.

    Secondary Outcome Measures

    Measure:Overall Survival (OS) (Part 2)
    Time Frame:Up to 45 months after the first participant is randomized
    Safety Issue:
    Description:OS is defined as the number of days from the date of randomization to the date of death from any cause.
    Measure:Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2)
    Time Frame:Up to 39 months after the first participant is randomized
    Safety Issue:
    Description:GRFS is defined as number of days from the date of randomization to occurrence of disease relapse OR occurrence or worsening of GvHD OR death from any cause.
    Measure:Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2)
    Time Frame:Up to 39 months after the first participant is randomized
    Safety Issue:
    Description:Time to deterioration defined as number of days from randomization to either deterioration of >= 5 points based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3 or death due to any cause.
    Measure:Graft-versus-Host Disease (GvHD) rate (Part 2)
    Time Frame:Up to 39 months after the first participant is randomized
    Safety Issue:
    Description:GvHD rate is defined as grade 2 or higher for acute graft-versus-host disease (aGvHD) and moderate/severe for chronic graft-versus-host disease (cGvHD) assessed by investigator
    Measure:Change From Randomization in Fatigue in Adult Participants (Part 2)
    Time Frame:Up to 39 months after the first participant is randomized
    Safety Issue:
    Description:Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.
    Measure:Minimal Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2)
    Time Frame:Up to 39 months after the first participant is randomized
    Safety Issue:
    Description:MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3 after initiation of treatment.

    Details

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

    Trial Keywords

    • Acute Myeloid Leukemia (AML)
    • Venetoclax
    • Azacitidine
    • Stem Cell Transplantation (SCT)
    • Best Support Care (BSC)
    • Cancer

    Last Updated

    January 16, 2020