Description:
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. Part 3 will be the Dose Finding portion to determine levels of venetoclax in
combination with Azacitidine (CC-486) to be explored. CC-486, and BSC may be administered for
up to 24 cycles.
Title
- Brief 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
- Official 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)
Clinical Trial IDs
- ORG STUDY ID:
M19-708
- SECONDARY ID:
2019-002217-19
- NCT ID:
NCT04102020
Conditions
- Acute Myeloid Leukemia (AML)
Interventions
| Drug | Synonyms | Arms |
|---|
| Venetoclax | ABT-199, GDC-0199 | Part 1: Venetoclax+Azacitidine (AZA)+Best Supportive Care |
| Azacitidine | | Part 1: Venetoclax+Azacitidine (AZA)+Best Supportive Care |
| Azacitidine (CC-486) | | Part 3: Venetoclax+ Azacitidine (CC-486)+Best Supportive Care |
Purpose
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. Part 3 will be the Dose Finding portion to determine levels of venetoclax in
combination with Azacitidine (CC-486) to be explored. CC-486, and BSC may be administered for
up to 24 cycles.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1: Venetoclax+Azacitidine (AZA)+Best Supportive Care | Experimental | 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). | |
| Part 2: Arm A: Venetoclax+Azacitidine (AZA)+BSC | Experimental | 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). | |
| Part 2: Arm B: Best Supportive Care (BSC) | Experimental | Participants will receive treatment as prescribed by their physician according to the best supportive care for up to 24 cycles (1 cycle = 28 days) | |
| Part 3: Venetoclax+ Azacitidine (CC-486)+Best Supportive Care | Experimental | Participants will be administered with venetoclax dose A Days 1-28) up to 24 cycles, CC-486 will be administered orally, QD on Days 1 to 21 of each 28-day cycle for up to 24 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days). | - Venetoclax
- Azacitidine (CC-486)
|
Eligibility Criteria
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 poor 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.
Exclusion Criteria:
- History of acute promyelocytic leukemia (APL).
- History of active central nervous system involvement with acute myeloid leukemia
(AML).
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of Participants With Dose-Limiting Toxicities (DLTs) (Part 1) |
| Time Frame: | Time from treatment of first participant to 20th participant reaching end of cycle 1, approximately 7 Months |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Overall Survival (OS) |
| Time Frame: | Time from treatment to death from any cause, up to approximately 3 years |
| Safety Issue: | |
| Description: | OS is defined as the number of days from the date of randomization to the date of death. |
| Measure: | Percentage of Participants Who Achieve Minimal Minimal Residual Disease (MRD) |
| Time Frame: | Measured From Baseline to approximately 3.5 years after the first participant is randomized |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 (Part 2) |
| Time Frame: | Measured From Baseline to approximately 3.5 years after the first participant is randomized |
| 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: | Change From Baseline in Patient Reported Outcomes (PRO) Fatigue Score Based on Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a (Part 2) |
| Time Frame: | Measured From Baseline to approximately 3.5 years after the first participant is randomized |
| Safety Issue: | |
| Description: | 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". |
| Measure: | Change From Baseline in Patient Reported Outcomes (PRO) in Items from EORTC QLQ-C30 between Arms A and B (Part 2) |
| Time Frame: | Measured From Baseline to approximately 3.5 years after the first participant is randomized |
| 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: | Change From Baseline in Patient Reported Outcomes (PRO) in Items from European Quality-of-Life-5 Dimesional-5-Level (EQ5D5L) Between Arms A and B (Part 2) |
| Time Frame: | Measured From Baseline to approximately 3.5 years after the first participant is randomized |
| Safety Issue: | |
| Description: | The EQ5D5L is a standardized instrument used to measure health-related quality of life that can be used in a wide range of health conditions and treatments. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Acute myeloid leukemia (AML)
- Venetoclax
- Azacitidine
- Maintenance Therapy
- Conventional Chemotherapy
- Best supportive care (BSC)
Last Updated
August 17, 2021
