Acute Myeloid Leukemia
Conditions
Keywords
Acute myeloid leukemia, Relapsed or refractory acute myeloid leukemia, Children, Decitabine, DACOGEN, Cytarabine
Brief summary
The purpose of this study is to examine the safety and efficacy of decitabine in sequential administration with cytarabine in children with relapsed or refractory acute myeloid leukemia (AML).
Detailed description
This is an open-label (identity of assigned study drug will be known) study to evaluate safety, efficacy, and pharmacokinetics (study of what the body does to a drug) of decitabine in sequential administration with cytarabine in children with relapsed or refractory AML. The study will determine the maximum tolerated dose of cytarabine that can be given following decitabine (Phase 1) and the response rate to this combination (Phase 2). Participants may enter a continuation phase of single agent-decitabine infusions for as long as such treatment would be considered beneficial. Serial pharmacokinetic samples will be collected and safety and efficacy will be monitored throughout the study.
Interventions
DRUGPhase1 and Phase 2: decitabine
20 mg/m2 administered by intravenous infusion over 1 hour once daily for 5 consecutive days (Day 1 to Day 5 of 28-day cycle)
DRUGPhase 1: cytarabine
1 g/m2, 2 g/m2, and 1.5 g/m2 dose levels administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of 28-day cycle) for the determination of the maximum tolerated dose
DRUGPhase 2: cytarabine
Phase 1 maximum tolerated dose administered by intravenous infusion over 4 hours daily for 5 consecutive days (Day 8 to Day 12 of 28-day cycle)
Sponsors
Janssen Research & Development, LLC
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Histological diagnosis of acute myeloid leukemia (AML) according to the World Health Organization (WHO) classification * Diagnosis of AML which has relapsed or is refractory to standard of care and no curative therapy exists * Karnofsky or Lansky score of at least 50 * Must be recovered from acute toxicity of any prior treatment * Must have adequate organ function according to protocol-defined criteria * Agrees to protocol-defined use of effective contraception * Female participants of childbearing potential must have a negative serum or urine pregnancy test at Day 1 of Cycle 1
Exclusion criteria
* Prior treatment with decitabine or azacitidine * Acute promyelocytic leukemia (M3 subtype in the French-American-British \[FAB\] classification system) * CNS3 disease * acute myeloid leukemia (AML) associated with congenital syndromes such as Down syndrome, Fanconi anemia, Bloom syndrome, Kostmann syndrome or Diamond-Blackfan anemia, or bone marrow failure associated with inherited syndromes * White blood cell count greater than 40x10\^9 cells/liter(L) * Known allergies, hypersensitivity, or intolerance to decitabine or cytarabine or their excipients * Contraindications to the use of cytarabine per local prescribing information or prior adverse reactions to cytarabine which would prevent further use * Currently enrolled in the treatment phase of an interventional investigational study * Female who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug (however, the period after which it becomes safe to become pregnant after the last dose of treatment is not known) * Male who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug * Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments * Any social or medical condition that in the investigator's opinion renders the participant unfit for study participation * History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease * History of human immunodeficiency virus (HIV) antibody positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine | Cycle 1 (42 days) | 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. |
| Phase 1 and 2: Total Clearance of Decitabine | 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 | Total clearance of drug after intravenously administration was calculated as: dose/area under the plasma concentration-time curve. |
| Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine | 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 | 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. |
| Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28 | Cycle 1 (28 days) Day 28 | 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. |
| Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28 | Cycle 2 (28 days) Day 28 | 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. |
| Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment | End of study treatment (approximately 3 years) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | 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. |
| Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Approximately 3 years 10 months | 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. |
| Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine | 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. |
| Phase 2: Duration of Response | From time of response to relapse, study completion/withdrawal, or death, whichever comes first, for up to approximately 3 years 10 months | Duration of response is defined as weeks from date of first response to date of first relapse or date of death. |
| Phase 2: Overall Response Rate | Up to approximately 3 years 10 months | 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. |
| Phase 1 and 2: Overall Survival (OS) | From enrollment to death or withdrawal, whichever comes first, for up to approximately 3 years 10 months | 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. |
| Phase 1 and 2: Event-Free Survival | From enrollment to progression/relapse, death, or withdrawal, whichever comes first, for up to approximately 3 years 10 months | 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. |
Countries
Belgium, Denmark, France, Germany, Netherlands, Spain, United Kingdom
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Dacogen + Cytarabine 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. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase 1 | Lack of Efficacy | 8 | 0 |
| Phase 1 | Other | 1 | 0 |
| Phase 2 | Lack of Efficacy | 0 | 4 |
| Phase 2 | Physician Decision | 0 | 1 |
| Phase 2 | Proceed To Transplant | 0 | 3 |
Baseline characteristics
| Characteristic | Dacogen + Cytarabine |
|---|---|
| Age, Continuous | 73.3 months STANDARD_DEVIATION 46.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment Belgium | 1 Participants |
| Region of Enrollment Denmark | 2 Participants |
| Region of Enrollment France | 4 Participants |
| Region of Enrollment Germany | 1 Participants |
| Region of Enrollment Netherlands | 1 Participants |
| Region of Enrollment Spain | 4 Participants |
| Region of Enrollment United Kingdom | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 9 | 6 / 8 |
| other Total, other adverse events | 9 / 9 | 8 / 8 |
| serious Total, serious adverse events | 4 / 9 | 4 / 8 |
Outcome results
Primary
Phase 1 and 2: Total Clearance of Decitabine
Total clearance of drug after intravenously administration was calculated as: dose/area under the plasma concentration-time curve.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Decitabine (Dacogen) + Cytarabine | 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 |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Total Clearance of Decitabine | Greater than (>) 2 to <= 6 years | 152.1 liter per hour per square meter |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Total Clearance of Decitabine | > 6 to <= 12 years | 125.9 liter per hour per square meter |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Total Clearance of Decitabine | > 12 to <= 16 years | 123.2 liter per hour per square meter |
Primary
Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine | > 1 month to <= 2 years | 35.9 liter per square meter |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine | > 2 to <= 6 years | 36.5 liter per square meter |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine | > 6 to <= 12 years | 31.8 liter per square meter |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine | > 12 to <= 16 years | 35.9 liter per square meter |
Primary
Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine
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.
Time frame: Cycle 1 (42 days)
Population: Population included participants who experienced a DLT by the end of Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine | 2 gram per square meter |
Primary
Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28 | 20 percentage of participants |
Primary
Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28 | 66.7 percentage of participants |
Primary
Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment
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.
Time frame: End of study treatment (approximately 3 years)
Population: Population included all enrolled participants evaluable in Phase 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment | 12.5 percentage of participants |
Secondary
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine
AUC is the area under the plasma concentration-time curve of decitabine.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine | > 1 month to <= 2 years | 124.8 nanogram*hour per milliliter (ng*h/mL) |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine | > 2 to <= 6 years | 131.5 nanogram*hour per milliliter (ng*h/mL) |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine | > 6 to <= 12 years | 158.9 nanogram*hour per milliliter (ng*h/mL) |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine | > 12 to <= 16 years | 162.4 nanogram*hour per milliliter (ng*h/mL) |
Secondary
Phase 1 and 2: Event-Free Survival
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Event-Free Survival | 1 days |
Secondary
Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine
Cmax is the maximum observed plasma concentration of Decitabine.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | > 1 month to <= 2 years | 118.4 nanogram per milliliter (ng/mL) |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | > 2 to <= 6 years | 123.1 nanogram per milliliter (ng/mL) |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | > 6 to <= 12 years | 148.7 nanogram per milliliter (ng/mL) |
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | > 12 to <= 16 years | 151.4 nanogram per milliliter (ng/mL) |
Secondary
Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | 17 Participants |
Secondary
Phase 1 and 2: Overall Survival (OS)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 1 and 2: Overall Survival (OS) | 5.1 months |
Secondary
Phase 2: Duration of Response
Duration of response is defined as weeks from date of first response to date of first relapse or date of death.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 2: Duration of Response | Participant 1 | 44.6 weeks |
| Decitabine (Dacogen) + Cytarabine | Phase 2: Duration of Response | Participant 2 | 6.3 weeks |
Secondary
Phase 2: Overall Response Rate
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.
Time frame: Up to approximately 3 years 10 months
Population: Population included all enrolled participants evaluable in Phase 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Decitabine (Dacogen) + Cytarabine | Phase 2: Overall Response Rate | 37.5 Percentage of participants |