Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Decitabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

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)

Phase1 and Phase 2: decitabine

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 1: 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)

Phase 2: cytarabine

Janssen Research & Development, LLC Clinical Trial

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.

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

Phase 1-2 Safety and Efficacy Study of DACOGEN in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia

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.

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

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.

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.

Cmax is the maximum observed plasma concentration of Decitabine.

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

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

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.

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.

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.

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.

Janssen Research & Development, LLC

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.

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 1): 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.

Phase 1 (Cohort 2) and Phase 2: 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.

Dacogen + Cytarabine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Belgium

Denmark

France

Germany

Netherlands

Spain

United Kingdom

Region of Enrollment

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

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.

Clinical Leader

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.

Decitabine (Dacogen) + Cytarabine

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

Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine

> 1 month to <= 2 years

> 2 to <= 6 years

> 6 to <= 12 years

> 12 to <= 16 years

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.

Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine

>1 month to less than or equal to (<=) 2 years

Greater than (>) 2 to <= 6 years

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.

Phase 1 and 2: Total Clearance of Decitabine

Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine

Participant 1

Participant 2

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.

Phase 2: Duration of Response

Population included all enrolled participants evaluable in Phase 2.

Phase 2: Overall Response Rate

Phase 1 and 2: Overall Survival (OS)

Phase 1 and 2: Event-Free Survival

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.

Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine

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.

Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28

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

Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28

Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment

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 1: Decitabine 20 mg/m^2 + Cytarabine 1 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).

Spots Global Cancer Trial Database for A Study of Decitabine (DACOGEN) in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia

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