Acute Myeloid Leukemia (AML), Cancer
Conditions
Keywords
Acute Myeloid Leukemia (AML), Venetoclax, Azacitidine, Stem Cell Transplantation (SCT), Best Support Care (BSC), Cancer
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).
Interventions
DRUGVenetoclax
Tablet; Oral
DRUGAzacitidine
Subcutaneous (SC) or intravenous (IV) injection
OTHERBest Supportive Care (BSC)
BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1) | Up to 28 days | DLTs were 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 approximately 41 months | OS was defined as the time from the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Morphologic Relapse-Free Survival (RFS) (Part 2) | Up to approximately 41 months | Morphologic relapse from AML was 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 the investigator. |
| Composite Relapse-Free Survival (RFS) (Part 2) | Up to approximately 41 months | Composite RFS was defined as the time from randomization from either morphologic relapse from AML, or non-morphologic relapse from AML, whichever comes first. Non-morphologic relapse from AML was 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 came first as determined by the investigator. |
| Graft-versus-Host Disease (GvHD)-Free, Relapse Free Survival (GRFS) (Part 2) | Up to approximately 41 months | GRFS was defined as the time from the date of randomization to occurrence of disease relapse or incidence of GvHD or death from any cause. |
| Rate of Participants Without Higher Grade of GvHD (Part 2) | 90 days after randomization | Rate of Participants without higher grade of GvHD was defined as the percentage of participants without grade 2 or higher for acute graft-versus-host disease (aGvHD) and moderate/severe for chronic graft-versus-host disease (cGvHD) assessed by investigator at 90 days after randomization. |
| Change From Baseline in Physical Functioning Subscore as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (Part 2) | Baseline, Month 6 | The EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales. The physical functioning score, reported here, ranged from 0 to 100, with a higher score indicating a better level of functioning. Positive changes from baseline indicate improvement. |
| Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a Score (Part 2) | Baseline, Month 6 | PROMIS Cancer Fatigue SF is a seven item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Not at all, 2 = A little bit, 3 = Somewhat, 4 = Quite a bit, and 5 = Very much. The total raw score is the sum of the responses to each question and is converted to a T-score. The T-score re-scales the total raw score to a standardized score with a mean of 50 and a standard deviation of 10. T-Scores range from 29.4 to 83.2, with higher scores indicating more fatigue. Negative changes from baseline indicate improvement. |
| Percentage of Participants With Measurable Residual Disease (MRD) Conversion in Participants With MRD >= 10^-3 at Baseline (Part 2) | Up to approximately 41 months | MRD conversion rate was defined as the percentage of participants who convert to MRD \< 10\^-3 after initiation of treatment. The population for MRD analysis included participants whose bone marrow was MRD positive (\>=10\^-3, as determined by central flow cytometry) at baseline prior to randomization. |
| Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2) | Up to approximately 41 months | Time to deterioration was defined as number of days from randomization to either deterioration of \>= 5 points based on the EORTC QLQ-C30 version 3 or death due to any cause. The GHS/QoL scale includes 2 questions in which participants were asked to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The 2 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. |
| Change From Baseline in European Quality-of-Life-5 Dimensional-5-Level (EQ-5D-5L) Score | Baseline, Month 6 | The EQ-5D-5L is a generic preference instrument that has been validated in numerous populations and has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems) with higher scores representing higher symptom burden. A negative change from baseline indicates improvement in health status. |
Countries
Australia, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Participant flow
Pre-assignment details
In Part 1, a total of 65 participants were screened and 35 participants received at least one dose of study drug. In Part 2, a total of 783 participants were screened, 430 were randomized, and 205 received at least one dose of study drug.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized < 18 | 5 Participants |
| Age, Customized >= 18 to < 65 | 356 Participants |
| Age, Customized >= 65 to < 75 | 97 Participants |
| Age, Customized >= 75 | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 127 Participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 30 | 3 / 5 | 46 / 216 | 56 / 214 |
| other Total, other adverse events | 30 / 30 | 5 / 5 | 179 / 216 | 200 / 214 |
| serious Total, serious adverse events | 9 / 30 | 2 / 5 | 66 / 216 | 97 / 214 |
Outcome results
None listed