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| ID | Type | Description | Link |
|---|---|---|---|
| DACOGENAML2004 | Other Identifier | Janssen Research & Development, LLC | |
| 2013-000390-70 | EudraCT Number |
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EMA/PDCO acknowledged that available results from this study do not support further clinical studies in relapsed/refractory AML paediatric patients.
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Decitabine and cytarabine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Phase1 and Phase 2: decitabine | Drug | 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) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Cycle 1 (42 days) |
| 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. | 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 |
| 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. | 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 |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | Cmax is the maximum observed plasma concentration 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 |
| Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ghent | Belgium | |||||
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1 |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 6, 2015 |
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| Phase 1: cytarabine | Drug | 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 |
|
| Phase 2: cytarabine | Drug | 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) |
|
| Cycle 1 (28 days) Day 28 |
| 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. | Cycle 2 (28 days) Day 28 |
| 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. | End of study treatment (approximately 3 years) |
AUC is the area under the plasma concentration-time curve 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 |
| 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. | From time of response to relapse, study completion/withdrawal, or death, whichever comes first, for up to approximately 3 years 10 months |
| 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. | Up to approximately 3 years 10 months |
| 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. | From enrollment to death or withdrawal, whichever comes first, for up to approximately 3 years 10 months |
| 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. | From enrollment to progression/relapse, death, or withdrawal, whichever comes first, for up to approximately 3 years 10 months |
| 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. | Approximately 3 years 10 months |
| Copenhagen Ø |
| Denmark |
| Paris | France |
| Toulouse | France |
| Vandœuvre-lès-Nancy | France |
| Essen | Germany |
| Hamburg | Germany |
| Hanover | Germany |
| Stuttgart | Germany |
| Rotterdam | Netherlands |
| Barcelona | Spain |
| Madrid | Spain |
| Valencia | Spain |
| Birmingham | United Kingdom |
| Cambridge | United Kingdom |
| Glasgow | United Kingdom |
| Sutton | United Kingdom |
| FG001 | 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). |
| COMPLETED |
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| NOT COMPLETED |
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| Phase 2 |
|
|
Population included all enrolled participants in Phase 1 and Phase 2.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | months |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Population included participants who experienced a DLT by the end of Cycle 1. | Posted | Number | gram per square meter | Cycle 1 (42 days) |
|
|
| ||||||||||||||||||||||||||
| Secondary | Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine | Cmax is the maximum observed plasma concentration of Decitabine. | 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. | Posted | Median | Full Range | nanogram per milliliter (ng/mL) | 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 |
|
| ||||||||||||||||||||||||||
| 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. | 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. | Posted | Median | Full Range | liter per hour per square meter | 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 |
|
| ||||||||||||||||||||||||||
| 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. | 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. | Posted | Median | Full Range | nanogram*hour per milliliter (ng*h/mL) | 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 |
|
| ||||||||||||||||||||||||||
| 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. | 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. | Posted | Number | weeks | From time of response to relapse, study completion/withdrawal, or death, whichever comes first, for up to approximately 3 years 10 months |
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| 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. | Population included all enrolled participants evaluable in Phase 2. | Posted | Number | Percentage of participants | Up to approximately 3 years 10 months |
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| 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. | Population included all enrolled participants in Phase 1 and Phase 2. | Posted | Median | 95% Confidence Interval | months | From enrollment to death or withdrawal, whichever comes first, for up to approximately 3 years 10 months |
|
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| 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. | Population included all enrolled participants in Phase 1 and Phase 2. | Posted | Median | Full Range | days | From enrollment to progression/relapse, death, or withdrawal, whichever comes first, for up to approximately 3 years 10 months |
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| 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. | 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. | Posted | Count of Participants | Participants | Approximately 3 years 10 months |
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| 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. | 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. | Posted | Median | Full Range | liter per square meter | 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 |
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| 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. | 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. | Posted | Number | percentage of participants | Cycle 1 (28 days) Day 28 |
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| 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. | Population included all enrolled participants evaluable in Phase 2. Here 'N' signifies number of participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | Cycle 2 (28 days) Day 28 |
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| 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. | Population included all enrolled participants evaluable in Phase 2. | Posted | Number | percentage of participants | End of study treatment (approximately 3 years) |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1 (Cohort 1): 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. 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. | 8 | 9 | 4 | 9 | 9 | 9 |
| EG001 | Phase 1 (Cohort 2) and Phase 2: Dacogen + Cytarabine | 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. | 6 | 8 | 4 | 8 | 8 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Complication Associated with Device | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Lung Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Skin Exfoliation | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Skin Hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Conjunctivitis Allergic | Eye disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Dry Eye | Eye disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Anal Inflammation | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Lip Haemorrhage | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Mouth Haemorrhage | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Tongue Haemorrhage | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Catheter Site Haemorrhage | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Face Oedema | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hepatocellular Injury | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hepatomegaly | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypogammaglobulinaemia | Immune system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Enterobacter Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Fungal Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hepatic Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Lung Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pneumonia Klebsiella | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pseudomonas Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Staphylococcal Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Allergic Transfusion Reaction | Injury, poisoning and procedural complications | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Post Procedural Complication | Injury, poisoning and procedural complications | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Adenovirus Test Positive | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Blood Albumin Decreased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Gamma-Glutamyltransferase Increased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hyperferritinaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Dizziness Postural | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Device Occlusion | Product Issues | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Depressed Mood | Psychiatric disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Vulvovaginal Inflammation | Reproductive system and breast disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Rhinitis Atrophic | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Butterfly Rash | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Decubitus Ulcer | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Erythema Multiforme | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Lividity | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Pruritus Generalised | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Skin Hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
The Sponsor terminated the study earlier than planned due to lack of efficacy with 8 evaluable participants in Phase 2 with no clinically meaningful anti-leukemic activity.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Leader | Janssen Research & Development, LLC | 844-434-4210 | ClinicalTrialDisclosure@its.jnj.com |
| Oct 12, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| Lack of Efficacy |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| France |
|
| Germany |
|
| Netherlands |
|
| Spain |
|
| United Kingdom |
|
|
|
| Participants |
|
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| Participants |
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| Units |
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| Counts |
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| Participants |
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| Participants |
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