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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04102020




Registration number
NCT04102020
Ethics application status
Date submitted
23/09/2019
Date registered
25/09/2019
Date last updated
12/06/2020

Titles & IDs
Public title
A Safety and Efficacy Study of Oral Venetoclax Tablets and Injectable Azacitidine Versus Best Supportive Care as Maintenance Therapy in Adult Participants With Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy to Evaluate Improvement in Relapse-Free Survival
Scientific title
Randomized, Open-label, 2-Arm, Multicenter, Phase 3 Study of Venetoclax and Azacitidine Versus Best Supportive Care as Maintenance Therapy for Patients With Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy (VIALE-M)
Secondary ID [1] 0 0
2019-002217-19
Secondary ID [2] 0 0
M19-708
Universal Trial Number (UTN)
Trial acronym
VIALE-M
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
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 with venetoclax dose A once daily (QD) (Days 1-28) up to 24 cycles, azacitidine (AZA) dose A QD on Days 1-5 of each 28 day cycle 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 dose A QD (Days 1-28) up to 24 cycles, azacitidine (AZA) dose A, on Days 1-5 of each 28-day cycle 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 best supportive care 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 and expectant management according to institutional standards excluding AML directed therapy. BSC will be determined for each participant by the investigator.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-Limiting Toxicities (DLTs) (Part 1) - DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax as described in the protocol and evaluated by the Investigator and the sponsor.
Timepoint [1] 0 0
Time from treatment of first participant to 20th participant reaching end of cycle 1, approximately 7 Months
Primary outcome [2] 0 0
Relapse-Free Survival (RFS) (Part 2) - RFS is defined as the number of days from randomization to the date of relapse or the date of death from any cause, whichever comes first.
Timepoint [2] 0 0
Time from treatment to relapse or death from any cause, up to approximately 3 years
Secondary outcome [1] 0 0
Overall Survival (OS) - OS is defined as the number of days from the date of randomization to the date of death.
Timepoint [1] 0 0
Time from treatment to death from any cause, up to approximately 3 years
Secondary outcome [2] 0 0
Percentage of Participants Who Achieve Minimal Minimal Residual Disease (MRD) - The MRD conversion rate is defined as the percentage of participants deemed MRD positive (= 10^-3) at study initiation who converted to MRD of < 10^-3 in the bone marrow after randomization or initiation of treatment.
Timepoint [2] 0 0
Measured From Baseline to approximately 3.5 years after the first participant is randomized
Secondary outcome [3] 0 0
Time to Deterioration in Global Health Status (GHS)/Quality-of Life (QoL) Score Based on European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30-Item (EORTC QLQ-C30) Scoring Manual. - 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."
Timepoint [3] 0 0
Measured From Baseline to approximately 3.5 years after the first participant is randomized
Secondary outcome [4] 0 0
Change From Baseline in Patient Reported Outcomes (PRO) Fatigue Score Based on Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a - Fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a. 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".
Timepoint [4] 0 0
Measured From Baseline to approximately 3.5 years after the first participant is randomized

Eligibility
Key inclusion criteria
- Diagnosis of newly diagnosed acute myeloid leukemia (AML).

- Participant meets the following disease activity criteria:

- Confirmation of AML by World Health Organization (WHO) criteria (2016) and have
confirmed complete remission (CR) or complete remission with incomplete blood
count recovery (CRi) following completion of planned induction and consolidation
chemotherapy.

- Achieved first CR + CRi within 4 months of enrollment or be no more than 75 days
since last dose of conventional therapy.

- AML has intermediate or adverse risk cytogenetics per National Comprehensive
Cancer Network (NCCN) 2016 criteria.

- Eastern Cooperative Oncology Group (ECOG) performance status <= 2.

- Participant must have adequate hematologic, renal, and liver function laboratory
values as described in the protocol.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of acute promyelocytic leukemia (APL).

- History of active central nervous system involvement with acute myeloid leukemia
(AML).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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St George Hospital /ID# 215416 - Kogarah
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Liverpool Hospital /ID# 215415 - Liverpool
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Wollongong Hospital /ID# 216071 - Wollongong
Recruitment hospital [4] 0 0
Gold Coast University Hospital /ID# 214650 - Southport
Recruitment hospital [5] 0 0
Barwon Health University Hospital Geelong /ID# 217921 - Geelong
Recruitment hospital [6] 0 0
Box Hill Hospital /ID# 217622 - Melbourne
Recruitment hospital [7] 0 0
Perth Blood Institute Ltd /ID# 217531 - Nedlands
Recruitment hospital [8] 0 0
Toowoomba Hospital /ID# 217922 - Toowoomba
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
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2170 - Liverpool
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2500 - Wollongong
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4215 - Southport
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3220 - Geelong
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3128 - Melbourne
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6009 - Nedlands
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4350 - Toowoomba
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country
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Commercial sector/Industry
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Roche-Genentech
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The main objective of this study is to evaluate safety and efficacy of venetoclax in
combination with azacitidine (AZA) and best supportive care (BSC) compared to BSC as
maintenance therapy in adult participants with acute myeloid leukemia (AML) in first
remission after conventional chemotherapy. This study will be conducted in two parts. Part 1
will be the Dose Confirmation portion to determine recommended Phase 3 dose of venetoclax in
combination with AZA. Part 2 will be the randomization portion to evaluate if venetoclax in
combination with AZA as maintenance therapy improves RFS comparing to BSC. Part 2 begins
after Part 1 is completed. During this study, participants will receive venetoclax and
azacitidine or best supportive care for approximately 2 years with study visits varying from
1-5 per month.
Trial website
https://clinicaltrials.gov/show/NCT04102020
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04102020