Trial Outcomes & Findings for A Study of Decitabine (DACOGEN) in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia (NCT NCT01853228)

Last Updated: 2019-06-17

Results Overview

The maximum tolerated dose (MTD) for cytarabine was based on the number of participants experiencing a dose-limiting toxicity (DLT) by the end of Cycle 1. A non-hematological DLT was defined as: any Grade \>=3 toxicity that persists for greater than (\>) 5 days or any Grade 2 toxicity that persists for \>7 days and that is intolerable to the participant. A hematological DLT was defined as Grade 4 neutropenia or thrombocytopenia due to a hypoplastic bone marrow at Day 42, in the absence of malignant infiltration. The nominal duration of each cycle was 28 days. However, participants who had not experienced bone marrow recovery at Day 28 were followed up to Day 42. Failure of marrow recovery (improvement to Grade 3) by Day 42 was considered a DLT. The maximum duration of Cycle 1 was therefore 42 days.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Cycle 1 (42 days)

Results posted on

2019-06-17

Participant Flow

Total 17 participants were enrolled in the study. 16 participants were enrolled in Phase 1 (9 participants in Cohort 1 and 7 participants in Cohort 2). 7 participants of Cohort 2 continued to Phase 2. One additional participant was enrolled in Phase 2 of the study, making a total of 8 participants evaluable in Phase 2.

Participant milestones

Participant milestones
Measure	Cohort 1: Decitabine 20 mg/m^2 + Cytarabine 1 g/m^2 Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle). In addition, participants received cytarabine 1 gram per square meter (g/m\^2) dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Cohort 1 of Phase 1.	Cohort 2: Decitabine 20 mg/m^2 + Cytarabine 2 g/m^2 Participants received decitabine 20 mg/m\^2 by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Cohort 2 of Phase 1. Participants who completed Phase 1 were continued in Phase 2 and received cytarabine at MTD determined in Phase 1 (2 g/m\^2) by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle).
Phase 1 STARTED	9	7
Phase 1 COMPLETED	0	7
Phase 1 NOT COMPLETED	9	0
Phase 2 STARTED	0	8
Phase 2 COMPLETED	0	0
Phase 2 NOT COMPLETED	0	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Decitabine 20 mg/m^2 + Cytarabine 1 g/m^2 Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle). In addition, participants received cytarabine 1 gram per square meter (g/m\^2) dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Cohort 1 of Phase 1.	Cohort 2: Decitabine 20 mg/m^2 + Cytarabine 2 g/m^2 Participants received decitabine 20 mg/m\^2 by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Cohort 2 of Phase 1. Participants who completed Phase 1 were continued in Phase 2 and received cytarabine at MTD determined in Phase 1 (2 g/m\^2) by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle).
Phase 1 Lack of Efficacy	8	0
Phase 1 Other	1	0
Phase 2 Physician Decision	0	1
Phase 2 Proceed To Transplant	0	3
Phase 2 Lack of Efficacy	0	4

Baseline Characteristics

A Study of Decitabine (DACOGEN) in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dacogen + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) (Cohort 1) and 2 g/m\^2 (Cohort 2) dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Age, Continuous	73.3 months STANDARD_DEVIATION 46.26 • n=93 Participants
Sex: Female, Male Female	4 Participants n=93 Participants
Sex: Female, Male Male	13 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants
Race (NIH/OMB) White	8 Participants n=93 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=93 Participants
Region of Enrollment Belgium	1 Participants n=93 Participants
Region of Enrollment Denmark	2 Participants n=93 Participants
Region of Enrollment France	4 Participants n=93 Participants
Region of Enrollment Germany	1 Participants n=93 Participants
Region of Enrollment Netherlands	1 Participants n=93 Participants
Region of Enrollment Spain	4 Participants n=93 Participants
Region of Enrollment United Kingdom	4 Participants n=93 Participants

PRIMARY outcome

Timeframe: Cycle 1 (42 days)

Population: Population included participants who experienced a DLT by the end of Cycle 1.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=6 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine	2 gram per square meter

PRIMARY outcome

Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 minute (min), 0.5 hour, 1 hour, and 2 hour after end of infusion

Population: Population included all enrolled participants in this study assessed for pharmacokinetics (PK). Pharmacokinetic analysis was planned to be reported for the overall participants including Phase 1 and 2. Here 'n' signifies number of participants analyzed for specified category.

Total clearance of drug after intravenously administration was calculated as: dose/area under the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Total Clearance of Decitabine >1 month to less than or equal to (<=) 2 years	160.6 liter per hour per square meter Interval 11.7 to 942.3
Phase 1 and 2: Total Clearance of Decitabine Greater than (>) 2 to <= 6 years	152.1 liter per hour per square meter Interval 19.5 to 1061.0
Phase 1 and 2: Total Clearance of Decitabine > 6 to <= 12 years	125.9 liter per hour per square meter Interval 13.3 to 951.3
Phase 1 and 2: Total Clearance of Decitabine > 12 to <= 16 years	123.2 liter per hour per square meter Interval 11.4 to 832.6

PRIMARY outcome

Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion

Population: Population included all enrolled participants in this study assessed for PK. Pharmacokinetic analysis was planned to be reported for the overall participants including Phase 1 and 2. Here 'n' signifies number of participants analyzed for specified category.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine > 1 month to <= 2 years	35.9 liter per square meter Interval 2.7 to 558.4
Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine > 2 to <= 6 years	36.5 liter per square meter Interval 1.4 to 535.0
Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine > 6 to <= 12 years	31.8 liter per square meter Interval 2.0 to 645.8
Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine > 12 to <= 16 years	35.9 liter per square meter Interval 2.8 to 578.9

PRIMARY outcome

Timeframe: Cycle 1 (28 days) Day 28

Population: Population included all enrolled participants evaluable in Phase 2. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Response rate (percentage of participants who achieved CR or CRi) was measured using international working group (IWG) criteria. Response rate is defined as complete remission (CR) or complete remission with incomplete blood count recovery (CRi) in children with relapsed or refractory acute myeloid leukemia. CRi is defined as morphologic CR with residual neutropenia (less than \[\<\] 1,000/microliter) or thrombocytopenia \<100,000/ microliter). CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (\>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (\>) 1,000/ microliter, platelet count of \>100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=5 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28	20 percentage of participants

PRIMARY outcome

Timeframe: Cycle 2 (28 days) Day 28

Population: Population included all enrolled participants evaluable in Phase 2. Here 'N' signifies number of participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=3 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28	66.7 percentage of participants

PRIMARY outcome

Timeframe: End of study treatment (approximately 3 years)

Population: Population included all enrolled participants evaluable in Phase 2.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=8 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment	12.5 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion

Cmax is the maximum observed plasma concentration of Decitabine.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine > 1 month to <= 2 years	118.4 nanogram per milliliter (ng/mL) Interval 17.6 to 1621.0
Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine > 2 to <= 6 years	123.1 nanogram per milliliter (ng/mL) Interval 15.6 to 1012.0
Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine > 6 to <= 12 years	148.7 nanogram per milliliter (ng/mL) Interval 16.5 to 1415.0
Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine > 12 to <= 16 years	151.4 nanogram per milliliter (ng/mL) Interval 19.1 to 1303.0

SECONDARY outcome

Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion

AUC is the area under the plasma concentration-time curve of decitabine.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine > 1 month to <= 2 years	124.8 nanogramhour per milliliter (ngh/mL) Interval 21.3 to 1708.0
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine > 2 to <= 6 years	131.5 nanogramhour per milliliter (ngh/mL) Interval 19.3 to 1028.0
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine > 6 to <= 12 years	158.9 nanogramhour per milliliter (ngh/mL) Interval 21.0 to 1508.0
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine > 12 to <= 16 years	162.4 nanogramhour per milliliter (ngh/mL) Interval 24.2 to 1747.0

SECONDARY outcome

Timeframe: From time of response to relapse, study completion/withdrawal, or death, whichever comes first, for up to approximately 3 years 10 months

Population: Population included all enrolled participants who achieved CR or CRi response in Phase 2. There was insufficient data to perform Kaplan Meier analysis, therefore individual data for each evaluable participant was reported.

Duration of response is defined as weeks from date of first response to date of first relapse or date of death.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=2 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 2: Duration of Response Participant 1	44.6 weeks
Phase 2: Duration of Response Participant 2	6.3 weeks

SECONDARY outcome

Timeframe: Up to approximately 3 years 10 months

Population: Population included all enrolled participants evaluable in Phase 2.

Overall response rate is defined as percentage of participants with complete remission (CR) +complete remission with incomplete blood count recovery (CRi)+partial remission (PR) per IWG Criteria. CRi: morphologic CR with residual neutropenia (less than \[\<\] 1,000/microliter) or thrombocytopenia \<100,000/microliter). CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (\>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (\>) 1,000/ microliter platelet count of \>100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment. PR: all the same hematologic values of a CR, but with a decrease of \>=50% of the percentage of blasts to 5% to 25% in the bone marrow aspirate.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=8 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 2: Overall Response Rate	37.5 Percentage of participants

SECONDARY outcome

Timeframe: From enrollment to death or withdrawal, whichever comes first, for up to approximately 3 years 10 months

Population: Population included all enrolled participants in Phase 1 and Phase 2.

OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Overall Survival (OS)	5.1 months Interval 3.1 to 11.4

SECONDARY outcome

Timeframe: From enrollment to progression/relapse, death, or withdrawal, whichever comes first, for up to approximately 3 years 10 months

Population: Population included all enrolled participants in Phase 1 and Phase 2.

Event free survival is defined as the time from first dose of study drug to relapse from CR, death, or second malignancy for participants who achieved CR. CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (\>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (\>) 1,000/ microliter platelet count of \>100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Event-Free Survival	1 days Interval 1.0 to 348.0

SECONDARY outcome

Timeframe: Approximately 3 years 10 months

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). This outcome measure was planned to be reported for the overall participants including Phase 1 and 2.

TEAEs are defined as adverse events with onset or worsening on or after date of first dose of study treatment. An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Outcome measures

Outcome measures
Measure	Decitabine (Dacogen) + Cytarabine n=17 Participants Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1. The maximum tolerated dose identified in Phase 1 was administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) in Phase 2.
Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)	17 Participants

Adverse Events

Phase 1 (Cohort 1): Dacogen + Cytarabine

Serious events: 4 serious events

Other events: 9 other events

Deaths: 8 deaths

Phase 1 (Cohort 2) and Phase 2: Dacogen + Cytarabine

Serious events: 4 serious events

Other events: 8 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1 (Cohort 1): Dacogen + Cytarabine n=9 participants at risk Participants received decitabine 20 milligram per square meter (mg/m\^2) by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of each 28-day cycle) in Phase 1. In addition, participants received cytarabine 1 gram per square meter (g/m\^2) and 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of each 28-day cycle) for the determination of the maximum tolerated dose in Phase 1.	Phase 1 (Cohort 2) and Phase 2: Dacogen + Cytarabine n=8 participants at risk Participants received decitabine 20 mg/m\^2 by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of a 28-day cycle) in Phase 1 and Phase 2. In addition, participants received cytarabine 2 g/m\^2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of a 28-day cycle) for the determination of the maximum tolerated dose in Cohort 2 of Phase 1 and continued to receive (2 g/m\^2) in Phase 2.
Blood and lymphatic system disorders Anaemia	0.00% 0/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	12.5% 1/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Blood and lymphatic system disorders Febrile Neutropenia	33.3% 3/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	25.0% 2/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Blood and lymphatic system disorders Neutropenia	0.00% 0/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	12.5% 1/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	12.5% 1/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Eye disorders Keratitis	0.00% 0/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	12.5% 1/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
General disorders Complication Associated with Device	11.1% 1/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	0.00% 0/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
General disorders Pyrexia	11.1% 1/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	12.5% 1/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Infections and infestations Lung Infection	0.00% 0/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	12.5% 1/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Infections and infestations Sepsis	0.00% 0/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	25.0% 2/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Skin and subcutaneous tissue disorders Skin Exfoliation	11.1% 1/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	0.00% 0/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	11.1% 1/9 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.	0.00% 0/8 • Screening up to end of study (approximately 3 years 10 months) The safety analysis set included all enrolled participants who received at least 1 dose of study drug (DACOGEN). The AE data was planned to be analyzed separately for Phase 1 (Cohort 1) and combined for participants in Phase 1 (Cohort 2) and Phase 2.

Other adverse events

Additional Information

Clinical Leader

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER