Trial Outcomes & Findings for 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). (NCT NCT01835587)

Last Updated: 2018-11-20

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

2 months (Cycles 1 and 2)

Results posted on

2018-11-20

Participant Flow

The multicenter study was conducted in the United States and the United Kingdom. Participants were enrolled at 5 study sites.

Participants with a confirmed diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received an allogeneic hematopoietic stem cell transplant (HSCT) were eligible to participate and begin study drug between 42 and 84 days post HSCT. One participant was enrolled into the study but discontinued before being treated.

Participant milestones

Participant milestones
Measure	CC-486 200 mg Days 1-7 (Cohort 1) Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 (Cohort 2) Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 (Cohort 3A) Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 (Cohort 3) Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Overall Study STARTED	3	4	4	19
Overall Study COMPLETED	1	0	2	10
Overall Study NOT COMPLETED	2	4	2	9

Reasons for withdrawal

Reasons for withdrawal
Measure	CC-486 200 mg Days 1-7 (Cohort 1) Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 (Cohort 2) Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 (Cohort 3A) Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 (Cohort 3) Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Overall Study Disease Recurrence or Relapse	0	3	0	3
Overall Study Withdrawal by Subject	2	0	0	3
Overall Study Adverse Event	0	0	2	2
Overall Study Death	0	0	0	1
Overall Study Miscellaneous	0	1	0	0

Baseline Characteristics

MDS Participants Have This Classification

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CC-486 200 mg Days 1-7 (Cohort 1) n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 (Cohort 2) n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 (Cohort 3A) n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 (Cohort 3) n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.	Total n=30 Participants Total of all reporting groups
Age, Continuous	68.3 Years STANDARD_DEVIATION 5.77 • n=3 Participants	47.8 Years STANDARD_DEVIATION 18.26 • n=4 Participants	61.8 Years STANDARD_DEVIATION 8.73 • n=4 Participants	60.8 Years STANDARD_DEVIATION 12.60 • n=19 Participants	60.0 Years STANDARD_DEVIATION 13.11 • n=30 Participants
Sex: Female, Male Female	1 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	4 Participants n=19 Participants	5 Participants n=30 Participants
Sex: Female, Male Male	2 Participants n=3 Participants	4 Participants n=4 Participants	4 Participants n=4 Participants	15 Participants n=19 Participants	25 Participants n=30 Participants
Race/Ethnicity, Customized Asian	0 Participants n=3 Participants	1 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=19 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized White	3 Participants n=3 Participants	3 Participants n=4 Participants	4 Participants n=4 Participants	18 Participants n=19 Participants	28 Participants n=30 Participants
Race/Ethnicity, Customized Not Collected or Reported	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	1 Participants n=19 Participants	1 Participants n=30 Participants
Diagnosis at Study Entry Acute Myeloid Leukemia	2 Participants n=3 Participants	4 Participants n=4 Participants	4 Participants n=4 Participants	16 Participants n=19 Participants	26 Participants n=30 Participants
Diagnosis at Study Entry Myelodysplastic Syndromes	1 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	3 Participants n=19 Participants	4 Participants n=30 Participants
MDS International Prognostic Scoring System (IPSS) Risk Classification INT-1	0 Participants n=1 Participants • MDS Participants Have This Classification	0 Participants MDS Participants Have This Classification	0 Participants MDS Participants Have This Classification	1 Participants n=3 Participants • MDS Participants Have This Classification	1 Participants n=4 Participants • MDS Participants Have This Classification
MDS International Prognostic Scoring System (IPSS) Risk Classification INT-2	1 Participants n=1 Participants • MDS Participants Have This Classification	0 Participants MDS Participants Have This Classification	0 Participants MDS Participants Have This Classification	1 Participants n=3 Participants • MDS Participants Have This Classification	2 Participants n=4 Participants • MDS Participants Have This Classification
MDS International Prognostic Scoring System (IPSS) Risk Classification High	0 Participants n=1 Participants • MDS Participants Have This Classification	0 Participants MDS Participants Have This Classification	0 Participants MDS Participants Have This Classification	1 Participants n=3 Participants • MDS Participants Have This Classification	1 Participants n=4 Participants • MDS Participants Have This Classification
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	1 Participants n=3 Participants	1 Participants n=4 Participants	1 Participants n=4 Participants	8 Participants n=19 Participants	11 Participants n=30 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1= Restrictive but ambulatory	2 Participants n=3 Participants	3 Participants n=4 Participants	3 Participants n=4 Participants	11 Participants n=19 Participants	19 Participants n=30 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but unable to work	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=4 Participants	0 Participants n=19 Participants	0 Participants n=30 Participants
Time from MDS or AML Diagnosis to Allogeneic HSCT	8.6 months STANDARD_DEVIATION 6.79 • n=3 Participants	6.4 months STANDARD_DEVIATION 4.35 • n=4 Participants	3.5 months STANDARD_DEVIATION 1.71 • n=4 Participants	10.6 months STANDARD_DEVIATION 16.72 • n=19 Participants	8.9 months STANDARD_DEVIATION 13.63 • n=30 Participants
AML World Health Organization (WHO) Classification AML With Recurrent Genetic Abnormalities	0 Participants:Participants n=3 Participants	2 Participants:Participants n=4 Participants	0 Participants:Participants n=4 Participants	7 Participants:Participants n=19 Participants	9 Participants:Participants n=30 Participants
AML World Health Organization (WHO) Classification AML With Myelodysplasia Related Changes	0 Participants:Participants n=3 Participants	0 Participants:Participants n=4 Participants	1 Participants:Participants n=4 Participants	2 Participants:Participants n=19 Participants	3 Participants:Participants n=30 Participants
AML World Health Organization (WHO) Classification Therapy related Myeloid Neoplasms	0 Participants:Participants n=3 Participants	0 Participants:Participants n=4 Participants	1 Participants:Participants n=4 Participants	0 Participants:Participants n=19 Participants	1 Participants:Participants n=30 Participants
AML World Health Organization (WHO) Classification AML Not Otherwise Specified	2 Participants:Participants n=3 Participants	2 Participants:Participants n=4 Participants	2 Participants:Participants n=4 Participants	7 Participants:Participants n=19 Participants	13 Participants:Participants n=30 Participants
Age, Categorical 18-64 years	0 Participants n=3 Participants	3 Participants n=4 Participants	3 Participants n=4 Participants	9 Participants n=19 Participants	15 Participants n=30 Participants
Age, Categorical 65-84 years	3 Participants n=3 Participants	1 Participants n=4 Participants	1 Participants n=4 Participants	10 Participants n=19 Participants	15 Participants n=30 Participants

PRIMARY outcome

Timeframe: 2 months (Cycles 1 and 2)

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

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
The Number of Participants With Dose Limiting Toxicities (DLT)	0 participants	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Number of Participants With Treatment Emergent Adverse Events (TEAE) Any TEAE	3 participants	4 participants	4 participants	19 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) Any TEAE With A Grade 3 or 4	2 participants	3 participants	3 participants	14 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) Any TEAE Related to IP	3 participants	3 participants	4 participants	17 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE With A Grade 3 or 4 Related to IP	1 participants	1 participants	3 participants	8 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) Serious TEAE	1 participants	3 participants	2 participants	6 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) Serious TEAE Related to IP	1 participants	0 participants	1 participants	2 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE With Outcome of Death	0 participants	0 participants	0 participants	1 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE Leading to Discontinuation of IP	0 participants	0 participants	2 participants	6 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE Related to IP and Leading to Stopping IP	0 participants	0 participants	1 participants	3 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE Leading to Dose Reduction	0 participants	0 participants	0 participants	1 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE Leading to Dose Interruption	1 participants	0 participants	1 participants	6 participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) TEAE Leading to Dose Drug Interruption/Reduction	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Percentage of Participants With Graft Versus Host Disease During the Entire Course of the Study	66.7 percentage of participants Interval 9.43 to 99.16	0.0 percentage of participants Interval 0.0 to 60.24	75.0 percentage of participants Interval 19.41 to 99.37	63.2 percentage of participants Interval 38.36 to 83.71

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Kaplan Meier Estimate of Time to Discontinuation From Treatment	189.0 Days Interval 184.0 to NA indicates time was not reached due to participants remaining in study until study closure.	177.0 Days Interval 104.5 to 189.0	NA Days Interval 228.5 to NA indicates time was not reached due to participants remaining in study until study closure	389.0 Days Interval 58.0 to NA indicates time was not reached due to participants remaining in study until study closure

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=20 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) Without Concomitant Meds	204.6 ng*h/mL Geometric Coefficient of Variation 63.0	253.3 ng*h/mL Geometric Coefficient of Variation 26.6	—	—
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) With Concomitant Meds	176.8 ng*h/mL Geometric Coefficient of Variation 69.0	226.7 ng*h/mL Geometric Coefficient of Variation 54.5	187.2 ng*h/mL Geometric Coefficient of Variation 34.19	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=18 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated to Infinity (AUC-inf; AUC0-∞) Of CC-486 Without Concomitant Meds	206.0 ng*h/mL Geometric Coefficient of Variation 62.8	218.4 ng*h/mL Geometric Coefficient of Variation NA Could not be calculated as sample size = 1.	—	—
Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated to Infinity (AUC-inf; AUC0-∞) Of CC-486 With Concomitant Meds	187.5 ng*h/mL Geometric Coefficient of Variation 70.1	232.5 ng*h/mL Geometric Coefficient of Variation 51.7	188.6 ng*h/mL Geometric Coefficient of Variation 33.5	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=20 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Maximum Observed Concentration (Cmax) Of CC-486 Without Concomitant Meds	151.9 ng/mL Geometric Coefficient of Variation 43.59	149.8 ng/mL Geometric Coefficient of Variation 7.6	—	—
Maximum Observed Concentration (Cmax) Of CC-486 With Concomitant Meds	114.3 ng/mL Geometric Coefficient of Variation 73.4	137.85 ng/mL Geometric Coefficient of Variation 65.7	91.49 ng/mL Geometric Coefficient of Variation 25.1	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=20 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Time to Reach Maximum Concentration (Tmax) of CC-486 Without Concomitant Meds	0.77 hours Interval 0.5 to 1.5	2.3 hours Interval 1.5 to 3.1	—	—
Time to Reach Maximum Concentration (Tmax) of CC-486 With Concomitant Meds	1.5 hours Interval 0.47 to 3.0	2.0 hours Interval 1.5 to 2.5	2.0 hours Interval 2.0 to 2.0	—

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=18 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Terminal Half-Life (T1/2) of CC-486 Without Concomitant Meds	0.528 hours Geometric Coefficient of Variation 6.8	0.575 hours Geometric Coefficient of Variation NA Could not be calculated since sample size = 1	—	—
Terminal Half-Life (T1/2) of CC-486 With Concomitant Meds	0.553 hours Geometric Coefficient of Variation 24.5	0.565 hours Geometric Coefficient of Variation 44.3	0.446 hours Geometric Coefficient of Variation 20.6	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=18 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Apparent Total Clearance (CL/F) of CC-486 Without Concomitant Meds	971.1 L/h Geometric Coefficient of Variation 62.8	1374 L/h Geometric Coefficient of Variation NA Could not be calculated since sample size = 1	—	—
Apparent Total Clearance (CL/F) of CC-486 With Concomitant Meds	1067 L/h Geometric Coefficient of Variation 70.1	1290 L/h Geometric Coefficient of Variation 51.7	795.4 L/h Geometric Coefficient of Variation 33.5	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=18 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=5 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=2 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Apparent Volume of Distribution (Vz/F) of CC-486 Without Concomitant Meds	739.9 Liters Geometric Coefficient of Variation 58.7	1139 Liters Geometric Coefficient of Variation NA Could not be calculated since sample size = 1	—	—
Apparent Volume of Distribution (Vz/F) of CC-486 With Concomitant Meds	851.3 Liters Geometric Coefficient of Variation 77.6	1052 Liters Geometric Coefficient of Variation 100.0	511.8 Liters Geometric Coefficient of Variation 12.3	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Percentage of Participants With Disease Relapse or Progression	33.3 Percentage of Participants	75.0 Percentage of Participants	0 Percentage of Participants	15.8 Percentage of Participants

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Time to Disease Recurrence/Progression	691.7 days Standard Deviation 436.10	452.5 days Standard Deviation 493.50	660.8 days Standard Deviation 218.12	521.7 days Standard Deviation 310.53

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Overall Survival	NA Days Interval 741.0 to NA as OS was not reached due to long survival of subjects relative to study duration.	NA Days Interval 303.5 to NA as OS was not reached due to long survival of subjects relative to study duration.	NA Days NA as OS was not reached due to long survival of subjects relative to study duration.	NA Days Interval 467.0 to NA as OS was not reached due to long survival of subjects relative to study duration.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg Days 1-7 n=3 Participants Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 n=4 Participants Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 n=4 Participants Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 n=19 Participants Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Kaplan Meier Estimate of Relapse-Free Survival (RFS)	921.0 Days Interval 741.0 to 1101.0	255.0 Days Interval 183.0 to NA as RFS was not reached due to long survival of subjects relative to study duration.	NA Days NA as RFS was not reached due to long survival of subjects relative to study duration.	NA Days Interval 281.0 to NA as RFS was not reached due to long survival of subjects relative to study duration.

Adverse Events

CC-486 200 mg Days 1-7 (Cohort 1)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

CC-486 300 mg Days 1-7 (Cohort 2)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 4 deaths

CC-486 150 mg Days 1-14 (Cohort 3A)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 2 deaths

CC-486 200 mg Days 1-14 (Cohort 3)

Serious events: 6 serious events

Other events: 18 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Anne McClain, Senior Manager

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission up to 90 additional days. Investigator must delete confidential data before submission or defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER

Measure	CC-486 200 mg Days 1-7 (Cohort 1) n=3 participants at risk Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death	CC-486 300 mg Days 1-7 (Cohort 2) n=4 participants at risk Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 150 mg Days 1-14 (Cohort 3A) n=4 participants at risk Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.	CC-486 200 mg Days 1-14 (Cohort 3) n=19 participants at risk Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death.
Blood and lymphatic system disorders Haemolysis	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Cardiac disorders Atrial fibrillation	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	10.5% 2/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Gastrointestinal disorders Nausea	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	10.5% 2/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Gastrointestinal disorders Vomiting	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	10.5% 2/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
General disorders Asthenia	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
General disorders Pyrexia	33.3% 1/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	50.0% 2/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Immune system disorders Graft versus host disease in gastrointestinal tract	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	15.8% 3/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Infections and infestations Appendicitis	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Infections and infestations Cytomegalovirus infection	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Infections and infestations Device related infection	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Infections and infestations Pneumonia	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Infections and infestations Respiratory tract infection	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Investigations Blood creatinine increased	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Nervous system disorders Haemorrhage intracranial	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	5.3% 1/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	10.5% 2/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Vascular disorders Hypotension	0.00% 0/3 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	25.0% 1/4 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.	0.00% 0/19 • From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.