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)
- Conditions
- Acute Myeloid Leukemia (AML)Cancer
- Interventions
- Registration Number
- NCT04161885
- Lead Sponsor
- AbbVie
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 465
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care Best Supportive Care (BSC) 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) Part 2: Arm B - Best Supportive Care (BSC) 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) Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC Best Supportive Care (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). Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care Venetoclax 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) Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care Azacitidine 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) Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC Venetoclax 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). Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC Azacitidine 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).
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1) 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) 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.
- Secondary Outcome Measures
Name Time Method Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2) 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.
Composite Relapse-Free Survival (RFS) (Part 2) 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) Rate (Part 2) 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 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) 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.
Measurable Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2) 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.
Change From Randomization in Fatigue in Adult Participants (Part 2) 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.
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) 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).
Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2) 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.
Morphologic Relapse-Free Survival (RFS) (Part 2) 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).
Trial Locations
- Locations (165)
Arizona Oncology - Scottsdale - Cancer Transplant Institute /ID# 239711
🇺🇸Scottsdale, Arizona, United States
University of Arizona Cancer Center - Tucson /ID# 242507
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences /ID# 239804
🇺🇸Little Rock, Arkansas, United States
City of Hope /ID# 213681
🇺🇸Duarte, California, United States
UCHSC Anschultz Cancer Pavilion /ID# 215618
🇺🇸Aurora, Colorado, United States
Colorado Blood Cancer Institute /ID# 215980
🇺🇸Denver, Colorado, United States
Mayo Clinic /ID# 239710
🇺🇸Jacksonville, Florida, United States
AdventHealth Medical Group Blood & Marrow Transplant at Orlando /ID# 213985
🇺🇸Orlando, Florida, United States
Ann & Robert H Lurie Children's Hospital of Chicago /ID# 215840
🇺🇸Chicago, Illinois, United States
The University of Chicago Medical Center /ID# 215616
🇺🇸Chicago, Illinois, United States
Scroll for more (155 remaining)Arizona Oncology - Scottsdale - Cancer Transplant Institute /ID# 239711🇺🇸Scottsdale, Arizona, United States