Safety Study of Oral Azacitidine (CC-486) as Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS).

A TEAE was defined as any AE with an onset date on or after the first dose of IP or any event already present that worsened in severity or increased in frequency after exposure to IP up to 28 days after the last dose. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.0, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above.

Time frame: From the first dose of investigational product (IP) up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall; up to the final data cut off date of 14 July 2017

Population: The safety population includes all participants who received at least one dose of IP.

A DLT included events that started within 28 days of the first dose of CC-486 in a 28-day cycle, constituted a change from baseline irrespective of outcome, as decided by the investigator to be related to CC-486 including: * ≥ Grade (GR) 3 nausea, diarrhea, or vomiting despite the use of medical support * Other significant nonhematologic toxicity of ≥ GR 3 considered not related to the disease or intercurrent illness • Absolute neutrophil count (ANC) \< 0.5 x 10\^9/L for \> 1 week despite growth factor support * Platelets \< 25 x 10\^9/L for \> 1 week despite transfusion support * Failure of recovery to an ANC ≥ 1.0 x 10\^9/L and/or platelets ≥ 50 x 10\^9/L with a hypocellular marrow by 56 days after the start of a cycle of CC-486 not due to relapse or progressive disease. The maximum tolerated dose is defined as the cohort delivering the highest dose in which no more than 33% of the evaluable subjects had a DLT The safety population included subjects who received ≥ 1 dose of CC-486

Time frame: 2 months (Cycles 1 and 2)

Population: The safety population included all participants who received at least one dose of investigational product.

Apparent total clearance, calculated as \[Dose/AUCinf\].

Time frame: On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.

Apparent volume of distribution, calculated as \[(CL/F)/λz\].Apparent volume of distribution, calculated as \[(CL/F)/λz\].

Time frame: On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.

Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as \[AUCt + Ct/ λz\]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.

Time frame: On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.

Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Time frame: On Day 1, pharmacokinetic (PK) samples were collected at predose and over a 6-hour period following drug administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose; Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.

Relapse-free survival was defined as the interval from the date of allogeneic HSCT to the date of first documented \> 5% blasts in the bone marrow or death from any cause, whichever occurs first. Participants who were still alive and continued to have less than or equal to 5% blasts in the bone marrow or who were lost to follow-up were censored at the date of their last response assessment.

Time frame: Date of allogenic HSCT to date of progression or death from any cause; Median number of days participants were assessed from first dose to last contact was 963 days for Cohort 1, 674.8 days for Cohort 2, 577.5 days for Cohort 3A and 553 days for Cohort 3

Population: Preliminary efficacy population includes all participants who received at least 1 dose of IP and had at least 1 post-baseline efficacy assessment performed. Participants who were still alive and continued to have ≤5% blasts in the bone marrow or who were lost to follow-up were censored at the date of their last response assessment.

The time to discontinuation from treatment was assessed as an estimate of treatment tolerability and was defined as the interval from the date of the first IP dose to the date of discontinuation from IP as indicated on the discontinuation from treatment Case Report Form page. Time to discontinuation from study treatment was analyzed using the Kaplan-Meier method where participants who did not discontinue were censored at the date of last visit.

Time frame: From the first dose of IP dose to the date of discontinuation from IP; the overall median time to discontinuation of IP was 283.5 days

Population: The safety population includes all participants who received at least one dose of investigational product. Participants who were on treatment at the time of study closure were censored at the date of last available visit

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Time frame: On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.

Overall Survival was defined as the time from the date of allogeneic hematopoietic stem cell transplantation to death from any cause.

Time frame: Date of the allogeneic HSCT to death from any cause. Median number of days participants were assessed from first dose to last contact was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3.

Population: Preliminary efficacy population includes all participants who received at least 1 dose of IP and had at least 1 post-baseline efficacy assessment performed. All participants were followed until drop-out, death, or study closure. Participants who dropped out or were alive at study closure were censored at the time of last contact, as appropriate.

Disease relapse was defined as the reappearance of \> 5% blasts in the bone marrow that persists for at least 4 weeks. Disease progression was defined as the reappearance of \> 10% of blasts in the bone marrow that persisted for at least 4 weeks.

Time frame: Date of first dose of IP to disease relapse or progression; up to data cut-off date of 14 July 2017; median number of days assessed was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3.

Population: Preliminary efficacy population included all participants who received at ≥ 1 dose of IP and had at ≥ 1 post-baseline efficacy assessment performed.

Acute graft versus host disease generally occurs after allogeneic hematopoietic stem cell transplantation. It is a reaction of donor immune cells against host tissues. The 3 main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract. Chronic GVHD is scored per the National Institute of Health consensus conference grading system. Clinical manifestations of chronic GVHD include skin involvement resembling lichen planus or the cutaneous manifestations of scleroderma; dry oral mucosa with ulcerations and sclerosis of the gastrointestinal tract; and a rising serum bilirubin concentration.

Time frame: From the first dose of CC-486 up to study discontinuation or death. Up to final data cut off date of 14 July 2017; up to 186 weeks and 4 days

Population: Safety population includes all participants who received at least 1 dose of IP.

Terminal phase half-life in plasma, calculated as \[(ln 2)/λz\]. t1/2 will only be calculated when a reliable estimate for λz can be obtained.

Time frame: On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.

Time to disease relapse/progression was defined as the interval from the date of allogeneic HSCT to the date of treatment discontinuation or study discontinuation where reason for discontinuation is disease relapse or disease progression, or the date of disease progression recorded on the survival electronic Case Report Form page, whichever occurred first. Time to disease relapse/progression was analyzed using competing risk methods where death without documented relapse/progression was treated as a competing risk for relapse/progression. relapse/progression.

Time frame: Date of allogenic HSCT to disease progression or relaopse; up to data cut-off date of 14 July 2017; median number of days assessed was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3.

Population: Preliminary efficacy population included all participants who received at ≥ 1 dose of IP and had at ≥ 1 post-baseline efficacy assessment performed. Participants who were lost to follow-up without documented relapse/progression, or were alive at last follow-up without documented relapse/progression were censored at the date of the last assessment.

Time to Cmax, obtained directly from the observed concentration versus time data.

Time frame: On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration.

Population: The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is \<1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined.