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) (VIALE-T)

• ClinicalTrials.gov Identifier: NCT04161885
• Recruitment Status: Active, not recruiting
• First Posted: November 13, 2019
• Last Update Posted: February 7, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: November 11, 2019
• First Posted Date: November 13, 2019
• Last Update Posted Date: February 7, 2024
• Actual Study Start Date: February 26, 2020
• Estimated Primary Completion Date: November 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 25, 2023)

• Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1) [ Time Frame: Up to the first treatment cycle (28 days) ]
  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.
• Overall Survival (OS) (Part 2) [ Time Frame: Up to 45 months after the first participant is randomized ]
  OS is defined as the number of days from the date of randomization to the date of death from any cause.

Original Primary Outcome Measures (submitted: November 11, 2019)

Relapse-Free Survival (RFS) [ Time Frame: Up to 39 months after the first participant is randomized ]

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.

Current Secondary Outcome Measures (submitted: July 25, 2023)

• Morphologic Relapse-Free Survival (RFS) (Part 2) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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).
• Composite Relapse-Free Survival (RFS) (Part 2) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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.
• Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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.
• Graft-versus-Host Disease (GvHD) Rate (Part 2) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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.
• 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) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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).
• Change From Randomization in Fatigue in Adult Participants (Part 2) [ Time Frame: Up to 39 months after the first participant is randomized ]
  Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.
• Measurable 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 ]
  MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3 after initiation of treatment.
• 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 ]
  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.
• 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) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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.

Original Secondary Outcome Measures (submitted: November 11, 2019)

• Overall Survival (OS) [ Time Frame: Up to 45 months after the first participant is randomized ]
  OS is defined as the number of days from the date of randomization to the date of death from any cause.
• Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) [ Time Frame: Up to 39 months after the first participant is randomized ]
  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.
• Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants [ Time Frame: Up to 39 months after the first participant is randomized ]
  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.
• Graft-versus-Host Disease (GvHD) rate [ Time Frame: Up to 39 months after the first participant is randomized ]
  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
• Change From Randomization in Fatigue in Adult Participants [ Time Frame: Up to 39 months after the first participant is randomized ]
  Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.
• Minimal Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization [ Time Frame: Up to 39 months after the first participant is randomized ]
  MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3 after initiation of treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)

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).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myeloid Leukemia (AML)
• Cancer

Intervention

• Drug: Venetoclax
  Tablet; Oral
  Other Names:

  • ABT-199
  • GDC-0199
  • VENCLEXTA
• Drug: Azacitidine
  Subcutaneous (SC) or intravenous (IV) injection
• Other: Best Supportive Care (BSC)
  BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.

Study Arms

• 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)
  Interventions:

  • Drug: Venetoclax
  • Drug: Azacitidine
  • Other: Best Supportive Care (BSC)
• 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).
  Interventions:

  • Drug: Venetoclax
  • Drug: Azacitidine
  • Other: Best Supportive Care (BSC)
• 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)
  Intervention: Other: Best Supportive Care (BSC)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 5, 2024): 465
• Original Estimated Enrollment (submitted: November 11, 2019): 424
• Estimated Study Completion Date: November 30, 2026
• Estimated Primary Completion Date: November 30, 2026 (Final data collection date for primary outcome measure)

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 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.

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Spain, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT04161885
• Other Study ID Numbers: M19-063; 2019-002621-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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.: No

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2024