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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04161885
Registration number
NCT04161885
Ethics application status
Date submitted
11/11/2019
Date registered
13/11/2019
Date last updated
7/02/2024
Titles & IDs
Public 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)
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Scientific 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)
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Secondary ID [1]
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2019-002621-30
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Secondary ID [2]
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M19-063
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Universal Trial Number (UTN)
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Trial acronym
VIALE-T
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML)
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Cancer
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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0
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine
Other interventions - Best Supportive Care (BSC)
Experimental: Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care - Participants 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)
Experimental: Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC - Participants 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).
Experimental: Part 2: Arm B - Best Supportive Care (BSC) - Participants will receive treatment as prescribed by their physician according to the BSC for up to 24 cycles (1 cycle = 28 days)
Treatment: Drugs: Venetoclax
Tablet; Oral
Treatment: Drugs: Azacitidine
Subcutaneous (SC) or intravenous (IV) injection
Other interventions: Best Supportive Care (BSC)
BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)
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Assessment method [1]
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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.
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Timepoint [1]
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Up to the first treatment cycle (28 days)
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Primary outcome [2]
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Overall Survival (OS) (Part 2)
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Assessment method [2]
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OS is defined as the number of days from the date of randomization to the date of death from any cause.
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Timepoint [2]
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Up to 45 months after the first participant is randomized
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Secondary outcome [1]
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Morphologic Relapse-Free Survival (RFS) (Part 2)
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Assessment method [1]
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Morphologic relapse from AML defined as bone marrow blasts of >= 5% or reappearance of blasts in the peripheral blood not attributable to any other cause (e.g., bone marrow regeneration) in at least 2 peripheral blood samples at least one week apart or development of extramedullary disease after achieving a complete remission (CR) or complete remission with incomplete count recovery (CRi); or the date of death from any cause, whichever comes first as determined by Independent Review Committee (IRC).
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Timepoint [1]
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Up to 39 months after the first participant is randomized
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Secondary outcome [2]
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Composite Relapse-Free Survival (RFS) (Part 2)
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Assessment method [2]
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Morphologic relapse from AML, non-morphologic relapse from AML, which is defined as increase in disease burden determined by standard methods with reappearance or acquisition of new findings with or without change in anti-leukemic treatment per investigator decision due to cytogenetic abnormalities or change in molecular marker or measurable residual disease by multiparameter flow with sensitivity to at least 10^-3; or the date of death from any cause, whichever comes first as determined by IRC.
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Timepoint [2]
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Up to 39 months after the first participant is randomized
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Secondary outcome [3]
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Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2)
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Assessment method [3]
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GRFS is defined as number of days from the date of randomization to occurrence of disease relapse OR incidence of GvHD OR death from any cause.
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Timepoint [3]
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Up to 39 months after the first participant is randomized
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Secondary outcome [4]
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Graft-versus-Host Disease (GvHD) Rate (Part 2)
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Assessment method [4]
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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.
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Timepoint [4]
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Up to 39 months after the first participant is randomized
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Secondary outcome [5]
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Change from Baseline in Physical Functioning as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (Part 2)
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Assessment method [5]
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The EORTC-QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participantts rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
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Timepoint [5]
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Up to 39 months after the first participant is randomized
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Secondary outcome [6]
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Change From Randomization in Fatigue in Adult Participants (Part 2)
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Assessment method [6]
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Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.
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Timepoint [6]
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Up to 39 months after the first participant is randomized
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Secondary outcome [7]
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Measurable Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2)
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Assessment method [7]
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MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3 after initiation of treatment.
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Timepoint [7]
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Up to 39 months after the first participant is randomized
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Secondary outcome [8]
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Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2)
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Assessment method [8]
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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.
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Timepoint [8]
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Up to 39 months after the first participant is randomized
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Secondary outcome [9]
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Change in Patient Reported Signs, Symptoms and Impact of Acute Myeloid Leukemia (AML) as Measured by the European Quality-of-Life-5 Dimensional-5-Level (EQ-5D-5L)
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Assessment method [9]
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The EQ-5D-5L is a generic preference instrument that has been validated in numerous population and has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. These dimensions are measured on a 5-point scale: with higher scores representing better functioning/quality of life and greater symptom burden.
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Timepoint [9]
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Up to 39 months after the first participant is randomized
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Eligibility
Key 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 Acute Myeloid Leukemia (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
60 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.
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Minimum age
12
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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, Myeloproliferative
neoplasm (only allowed if it transformed to AML and AML should be the indication for
marrow transplantation).
- 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/02/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
30/11/2026
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Actual
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Sample size
Target
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Accrual to date
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Final
465
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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Recruitment hospital [1]
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The Kinghorn Cancer Centre /ID# 214660 - Darlinghurst
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Recruitment hospital [2]
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Royal Adelaide Hospital /ID# 215678 - Adelaide
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Recruitment hospital [3]
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Peter MacCallum Cancer Ctr /ID# 214653 - Melbourne
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Recruitment hospital [4]
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Alfred Health /ID# 240931 - Melbourne
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Recruitment postcode(s) [1]
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2010 - Darlinghurst
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Recruitment postcode(s) [2]
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5000 - Adelaide
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Recruitment postcode(s) [3]
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3000 - Melbourne
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Recruitment postcode(s) [4]
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3004 - Melbourne
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Recruitment outside Australia
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Switzerland
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State/province [98]
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Zuerich
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Taiwan
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Kaohsiung
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Country [100]
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Taiwan
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State/province [100]
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Taichung
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Country [101]
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Taiwan
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State/province [101]
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Taipei City
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Country [102]
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Taiwan
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State/province [102]
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Taipei
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Country [103]
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Taiwan
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State/province [103]
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Taoyuan City
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Country [104]
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United Kingdom
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State/province [104]
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Scotland
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Country [105]
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United Kingdom
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State/province [105]
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Birmingham
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Country [106]
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United Kingdom
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State/province [106]
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London
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Country [107]
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United Kingdom
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State/province [107]
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Newcastle upon Tyne
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
AbbVie
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Ethics approval
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Summary
Brief summary
The main objective of this study is to evaluate the efficacy of venetoclax in combination
with azacitidine to improve Overall Survival (OS) in Acute Myeloid Leukemia (AML)
participants 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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04161885
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Public notes
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Contacts
Principal investigator
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ABBVIE INC.
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Address
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AbbVie
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04161885
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