Acute Myeloid Leukemia
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of oral azacitidine plus best supportive care versus best supportive care as maintenance therapy in a cohort of Japanese participants ≥ 55 years of age with Acute Myeloid Leukemia (AML) and in complete remission/complete remission with incomplete blood count recovery after conventional induction chemotherapy with or without consolidation chemotherapy.
Interventions
DRUGOral Azacitidine
Specified dose on specified days
OTHERPlacebo
Specified dose of specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 55 years of age inclusive at the time of signing the informed consent * Newly diagnosed, histologically confirmed de novo Acute Myeloid Leukemia (AML) or AML secondary to prior myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) * Should have undergone induction therapy with intensive chemotherapy with or without consolidation therapy as recommended in appropriate guideline(s) or equivalent regimen according to institutional standard: having achieved first complete remission (CR)/complete remission with incomplete blood count recovery (CRi) status within 4 months prior to starting study therapy
Exclusion criteria
* Suspected or proven acute promyelocytic leukemia; or AML with previous hematologic disorder such as chronic myeloid leukemia or myeloproliferative neoplasms, excluding MDS and CMML * Prior bone marrow or stem cell transplantation * Received therapy with hypomethylating agents for MDS and went on to develop AML within four months of discontinuing the therapy with hypomethylating agents * Have achieved CR/CRi following therapy with hypomethylating agents Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence Free Survival (RFS) | Approximately 17.7 months | The time from randomization to the date of documented relapse after CR or CRi per central review, or death from any cause, whichever occurs first. Participants who are still alive without documented relapse after CR or CRi, or who were lost to follow-up without documented relapse, will be censored at the date of their last response assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Evaluation: AUC(0-T) | on C1D1 (after first dose on day 1) | Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration. |
| Pharmacokinetic Evaluation: AUC(INF) | on C1D1 (after first dose on day 1) | — |
| Pharmacokinetic Evaluation: CMax | on C1D1 (after first dose on day 1) | Cmax is defined as maximum plasma concentration of the drug. |
| Overall Survival (OS) | Approximately 17.7 months | The time from randomization to death from any cause and will be calculated using the randomization date and date of death, or date of last follow-up for censored participants. All participants will be followed until dropout, death, or study termination. Participants who dropout or are alive at study termination will have their OS times censored at the time of last contact, as appropriate. |
| Time to Relapse From CR or CRi | Approximately 17.7 months | The interval from the date of randomization to the date of documented relapse after CR or CRi, as defined according to the IWG AML response criteria. Time to relapse will be analyzed using a competing risk analysis where death without documented relapse is treated as a competing risk for relapse from CR/CRi. Similar censoring rules as in primary analysis of RFS will be applied. |
| Time to Discontinuation | Approximately 17.7 months | The interval from the date of randomization to the date of discontinuation from IP. Subjects who are ongoing in treatment at the time of study closure will be censored at the date of last visit. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Approximately 17.7 months | — |
| Number of Participants With Clinically Significant Changes in Physical Examination | Approximately 17.7 months | Number of participants with clinically significant changes in physical examination |
| Number of Participants With Clinically Significant Changes in Vital Signs | Approximately 17.7 months | Vital signs include the following: systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, temperature and weight. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Examinations | Approximately 17.7 months | — |
| Number of Participants Who Received Concomitant Medication | Approximately 17.7 months | Concomitant medications are defined as non-study medications that are started after the date of randomization but before the end of the study treatment period or started on or before the date of randomization but ended or remain ongoing during the study treatment period. |
| Mean Change From Baseline in Facit-Fatigue Scale | From C1D1 to C12D1 (approximately 336 days) | The FACIT-Fatigue Scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during usual daily activities over the past week. The level of fatigue is measured on a five-point Likert scale (0 = not at all fatigued to 4 = very much fatigued). It has scores that range from 0 to 52, with higher scores indicating less fatigue. Quality of life (QoL)scores on these FACIT scales significantly decline as patient performance status worsens. |
| Mean Change From Baseline in EQ-5D-5L | From C1D1 to C12D1 (approximately 336 days) | The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index (HUI) is assessed using the Crosswalk algorithm for France based on the individual responses to the 5 EQ-5D-5L domains ranging from -0.530 to 1.000. The smallest change considered clinically meaningful, is defined as a score difference of 0.08 points. The lower the score the better. |
| Pharmacokinetic Evaluation: T-Half | on C1D1 (after first dose on day 1) | the time required for the amount or concentration of a drug to decrease by one-half |
| Pharmacokinetic Evaluation: CLT/F(INF) | on C1D1 (after first dose on day 1) | the volume of plasma from which a substance is completely removed per unit time. |
| Pharmacokinetic Evaluation: Tmax | on C1D1 (after first dose on day 1) | Tmax is defined is the time to maximum plasma concentration |
| Pharmacokinetic Evaluation: Vz/F | on C1D1 (after first dose on day 1) | the amount of drug in the body to the concentration of drug measured in a biological fluid |
Countries
Japan, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
19 Participants randomized and treated
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.4 Years STANDARD_DEVIATION 4.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 0 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 2 / 7 |
| other Total, other adverse events | 12 / 12 | 7 / 7 |
| serious Total, serious adverse events | 4 / 12 | 2 / 7 |
Outcome results
None listed