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).
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).
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)
Completion Date
Completion Date Type
Estimated
Conditions
Acute Myeloid Leukemia (AML)
Cancer
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
Acute Myeloid Leukemia (AML)
Venetoclax
Azacitidine
Stem Cell Transplantation (SCT)
Best Support Care (BSC)
Cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT04161885
Org Class
Industry
Org Full Name
AbbVie
Org Study Id
M19-063
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)
Outcome Time Frame
Up to the first treatment cycle (28 days)
Outcome Description
OS is defined as the number of days from the date of randomization to the date of death from any cause.
Outcome Measure
Overall Survival (OS) (Part 2)
Outcome Time Frame
Up to 45 months after the first participant is randomized
Secondary Ids
Secondary Id
2023-507222-17-00
Secondary Outcomes
Outcome Description
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).
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Morphologic Relapse-Free Survival (RFS) (Part 2)
Outcome Description
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.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Composite Relapse-Free Survival (RFS) (Part 2)
Outcome Description
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.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2)
Outcome 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.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Graft-versus-Host Disease (GvHD) Rate (Part 2)
Outcome Description
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).
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
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)
Outcome Description
Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Change From Randomization in Fatigue in Adult Participants (Part 2)
Outcome Description
MRD conversion rate is defined as percentage of participants who convert to MRD \< 10\^-3 after initiation of treatment.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Measurable Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2)
Outcome 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.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2)
Outcome Description
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.
Outcome Time Frame
Up to 39 months after the first participant is randomized
Outcome Measure
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)
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
MeSH Terms
LEUKEMIA, MYELOID, ACUTE
NEOPLASMS
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
VENETOCLAX
AZACITIDINE
AZA COMPOUNDS
ORGANIC CHEMICALS
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
RIBONUCLEOSIDES