TriangleNCT00866281 · STUDY IN CONTEXT
A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
Draft scope assessment: unclear. Attached because the study's own record describes refractory disease. The study was not selected for this indication by its sponsor, and its eligibility has not been reconciled against this page in full. Found because this study's registry identifier is printed in an FDA approval notice, an FDA product label or an NCI summary held by this site. The citing document and the exact position of the identifier inside it are recorded. Being cited is not a statement that the study supports this treatment.
Read the full study record and all posted results →
Linked outcomes
MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT), based on a Bayesian logistic regression model (BLRM) employing the escalation with overdose control (EWOC) principle. A DLT was defined as a grade 3 or 4 non-hematological adverse event (AE) or abnormal laboratory value related to study drug. Mean and the 95% posterior probability estimates of having a DLT by age strata and dose is presented. Estimation of MTD and/or recommended dose for expansion (RDE) at the dose-escalation phase of the study was based upon the estimation of the probability of DLT for participants in the dose-determining set (DDS).
The best overall clinical response was determined as per the clinical assessment done by the investigator. Responders were defined as all participants with a best clinical response of leukemia free state, morphological complete remission, incomplete morphological complete remission, partial remission, bone marrow blast response, bone marrow minor blast response, peripheral blood blast response, minor peripheral blood blast response. Participants with stable disease, progressive disease and with missing tumour assessment or who discontinued the study or who died before having their first assessment were considered as non-responders. Stable disease was defined as failure to achieve any of the above response. Progressive disease was defined as doubling of the bone marrow blast percentage from baseline in participants with \<40% bone marrow blasts at baseline, or a 50% increase in bone marrow blast percentage from baseline in participants with \>40% bone marrow blasts at baseline,
Time to response was defined as the time from the date of start of midostaurin treatment to the date of first response. The best overall clinical response was determined as per the clinical assessment done by the investigator. Responders were defined as all participants with a best clinical response of leukemia free state, morphological complete remission, incomplete morphological complete remission, partial remission, bone marrow blast response, bone marrow minor blast response, peripheral blood blast response, minor peripheral blood blast response. Time to response was calculated by using the formula = (date of first response -date of start of midostaurin) +1 day.
Overall survival (OS) was defined as the time from start of treatment to date of death due to any cause. The percentage (%) event-free probability estimates were obtained from the Kaplan-Meier survival estimates.
The plasma concentrations of midostaurin (PKC412) and its two major metabolites, CGP62221 and CGP52421 were determined by using a validated liquid chromatography/tandem mass spectrometry method.
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes. Treatment related AEs or SAEs were defined as AEs or SAEs that were suspected to be related to study treatment as per investigator. On treatment death was a fatal event leading to permanent cessations of all vital functions of the body.
Reported safety
Quality of life and patient-reported measures
No linked quality-of-life measure is recorded for this setting and study.
Full draft applicability and source-link record
- trial
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- trial label
- A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
- applicability
- unclear
- applicability note
- Attached because the study's own record describes refractory disease. The study was not selected for this indication by its sponsor, and its eligibility has not been reconciled against this page in full.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- provenance class
- regulator-cited
- discovery note
- Found because this study's registry identifier is printed in an FDA approval notice, an FDA product label or an NCI summary held by this site. The citing document and the exact position of the identifier inside it are recorded. Being cited is not a statement that the study supports this treatment.
- outcome Count
- 6
- harms Count
- 2
- qol Count
- 0
- outcomes
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0000
- source section id
- NCT00866281-om-0000
- source outcome index
- 0
- endpoint
- Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT
- endpoint definition
- MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT), based on a Bayesian logistic regression model (BLRM) employing the escalation with overdose control (EWOC) principle. A DLT was defined as a grade 3 or 4 non-hematological adverse event (AE) or abnormal laboratory value related to study drug. Mean and the 95% posterior probability estimates of having a DLT by age strata and dose is presented. Estimation of MTD and/or recommended dose for expansion (RDE) at the dose-escalation phase of the study was based upon the estimation of the probability of DLT for participants in the dose-determining set (DDS).
- time origin
- Baseline, End of dose escalation phase (6 months)
- analysis role
- primary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- The analysis was performed in dose determining set (DDS) population. Here, 'n' signifies the number of evaluable participants for this measure.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0001
- source section id
- NCT00866281-om-0001
- source outcome index
- 1
- endpoint
- Percentage of Participants With Best Overall Response by Indication
- endpoint definition
- The best overall clinical response was determined as per the clinical assessment done by the investigator. Responders were defined as all participants with a best clinical response of leukemia free state, morphological complete remission, incomplete morphological complete remission, partial remission, bone marrow blast response, bone marrow minor blast response, peripheral blood blast response, minor peripheral blood blast response. Participants with stable disease, progressive disease and with missing tumour assessment or who discontinued the study or who died before having their first assessment were considered as non-responders. Stable disease was defined as failure to achieve any of the above response. Progressive disease was defined as doubling of the bone marrow blast percentage from baseline in participants with \<40% bone marrow blasts at baseline, or a 50% increase in bone marrow blast percentage from baseline in participants with \>40% bone marrow blasts at baseline,
- time origin
- Baseline, Day 15 (Day 1 of Cycle 2), Day 22 (Day 8 of Cycle 2), Day 29(Day 1 of Cycle 9), End of treatment (up to 24 months after last dose or until death whichever occurred first)
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- The analysis was performed in full analysis set (FAS) population, defined as all participants to whom study treatment was assigned.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0002
- source section id
- NCT00866281-om-0002
- source outcome index
- 2
- endpoint
- Time to Response With Midostaurin
- endpoint definition
- Time to response was defined as the time from the date of start of midostaurin treatment to the date of first response. The best overall clinical response was determined as per the clinical assessment done by the investigator. Responders were defined as all participants with a best clinical response of leukemia free state, morphological complete remission, incomplete morphological complete remission, partial remission, bone marrow blast response, bone marrow minor blast response, peripheral blood blast response, minor peripheral blood blast response. Time to response was calculated by using the formula = (date of first response -date of start of midostaurin) +1 day.
- time origin
- Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first)
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- The analysis was performed in FAS population. Here, "Number of participants analysed" signifies number of responders at specified time points for each arm, respectively.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0003
- source section id
- NCT00866281-om-0003
- source outcome index
- 3
- endpoint
- Overall Survival With Midostaurin
- endpoint definition
- Overall survival (OS) was defined as the time from start of treatment to date of death due to any cause. The percentage (%) event-free probability estimates were obtained from the Kaplan-Meier survival estimates.
- time origin
- Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first)
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- The analysis was performed in FAS population.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0004
- source section id
- NCT00866281-om-0004
- source outcome index
- 4
- endpoint
- Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221
- endpoint definition
- The plasma concentrations of midostaurin (PKC412) and its two major metabolites, CGP62221 and CGP52421 were determined by using a validated liquid chromatography/tandem mass spectrometry method.
- time origin
- Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3)
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- The analysis was performed in pharmacokinetic (PK) set population defined as all safety set participants who had at least one valid (measurable) PK sample of midostaurin, and who had no significant restricted co-medications.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0005
- source section id
- NCT00866281-om-0005
- source outcome index
- 5
- endpoint
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs or SAEs and Death During the Study
- endpoint definition
- An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes. Treatment related AEs or SAEs were defined as AEs or SAEs that were suspected to be related to study treatment as per investigator. On treatment death was a fatal event leading to permanent cessations of all vital functions of the body.
- time origin
- Baseline (start of study treatment) up to End of treatment (up to 24 months after last dose or until death whichever occurred first)
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- The analysis was performed in safety set population, defined as the participants who received at least one dose of midostaurin.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- arms
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0000
- arm key
- OG000
- arm label
- Cohort 1: Midostaurin (30 Milligrams/Meters^2)
- regimen
- Participants received bodyweight and BSA stratified dose of midostaurin 30 mg/m\^2 bid through oral route. The total daily dose in 30 mg/m\^2 bid cohort was 60 mg/m\^2.
- analyzed count
- 6
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0000#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0000
- arm key
- OG001
- arm label
- Cohort 2: Midostaurin (60 mg/m^2)
- regimen
- Participants received bodyweight and BSA stratified dose of midostaurin 60 mg/m\^2 bid through oral route. The total daily dose in 60 mg/m\^2 bid cohort was 120 mg/m\^2.
- analyzed count
- 11
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0000#groups/OG001
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0001
- arm key
- OG000
- arm label
- AML Subjects
- regimen
- Subjects with acute myeloid leukemia (AML) and received body-weight stratified dosage midostaurin 30 or 60 mg/m\^2.
- analyzed count
- 9
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0001#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0001
- arm key
- OG001
- arm label
- MLLr-ALL Subjects
- regimen
- Subjects with mixed lineage leukemia gene- rearranged acute lymphoblastic leukemia (MLLr-ALL) and received body-weight stratified dosage midostaurin 30 or 60 mg/m\^2.
- analyzed count
- 13
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0001#groups/OG001
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0002
- arm key
- OG000
- arm label
- AML Subjects
- regimen
- Subjects with acute myeloid leukemia (AML) and received body-weight stratified dosage midostaurin 30 or 60 mg/m\^2.
- analyzed count
- 5
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0002#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0002
- arm key
- OG001
- arm label
- MLLr-ALL Subjects
- regimen
- Subjects with mixed lineage leukemia gene- rearranged acute lymphoblastic leukemia (MLLr-ALL) and received body-weight stratified dosage midostaurin 30 or 60 mg/m\^2.
- analyzed count
- 3
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0002#groups/OG001
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0003
- arm key
- OG000
- arm label
- AML Subjects
- regimen
- Subjects with acute myeloid leukemia (AML) and received body-weight stratified dosage midostaurin 30 or 60 mg/m\^2.
- analyzed count
- 9
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0003#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0003
- arm key
- OG001
- arm label
- MLLr-ALL Subjects
- regimen
- Subjects with mixed lineage leukemia gene- rearranged acute lymphoblastic leukemia (MLLr-ALL) and received body-weight stratified dosage midostaurin 30 or 60 mg/m\^2.
- analyzed count
- 13
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0003#groups/OG001
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0004
- arm key
- OG000
- arm label
- Cohort 1: Midostaurin (30 Milligrams/Meters^2)
- regimen
- Participants received bodyweight and body surface area (BSA) stratified dose of midostaurin 30 mg/m\^2 bid through oral route. The total daily dose in 30 mg/m\^2 bid cohort was 60 mg/m\^2.
- analyzed count
- 7
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0004#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0004
- arm key
- OG001
- arm label
- Cohort 2: Midostaurin (60 mg/m^2)
- regimen
- Participants received bodyweight and BSA stratified dose of midostaurin 60 mg/m\^2 bid through oral route. The total daily dose in 60 mg/m\^2 bid cohort was 120 mg/m\^2.
- analyzed count
- 15
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0004#groups/OG001
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0005
- arm key
- OG000
- arm label
- Cohort 1: Midostaurin (30 Milligrams/Meters^2)
- regimen
- Participants received bodyweight and BSA stratified dose of midostaurin 30 mg/m\^2 bid through oral route. The total daily dose in 30 mg/m\^2 bid cohort was 60 mg/m\^2.
- analyzed count
- 7
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0005#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- outcome key
- om-0005
- arm key
- OG001
- arm label
- Cohort 2: Midostaurin (60 mg/m^2)
- regimen
- Participants received bodyweight and BSA stratified dose of midostaurin 60 mg/m\^2 bid through oral route. The total daily dose in 60 mg/m\^2 bid cohort was 120 mg/m\^2.
- analyzed count
- 15
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT00866281-om-0005#groups/OG001
- harms
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- harm key
- EG000
- source section id
- NCT00866281-ae
- event group key
- EG000
- event group label
- Cohort 1: Midostaurin (30 Milligrams/Meters^2)
- serious affected
- 3
- serious at risk
- 7
- other affected
- 6
- other at risk
- 7
- frequency threshold
- 5
- collection period
- Serious Adverse Events are monitored from date of First Participant First Visit (FPFV) up to Last Participant Last Visit (LPLV), 24 weeks and all other adverse events are monitored from First Participant First Treatment (FPFT) up to LPLV, 20 weeks
- event definition
- Source null
- undenominated note
- Source null
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-acute-lymphoblastic-leukemia-gleevec-579b72c1
- nct id
- NCT00866281
- harm key
- EG001
- source section id
- NCT00866281-ae
- event group key
- EG001
- event group label
- Cohort 2: Midostaurin (60 mg/m^2)
- serious affected
- 6
- serious at risk
- 15
- other affected
- 15
- other at risk
- 15
- frequency threshold
- 5
- collection period
- Serious Adverse Events are monitored from date of First Participant First Visit (FPFV) up to Last Participant Last Visit (LPLV), 24 weeks and all other adverse events are monitored from First Participant First Treatment (FPFT) up to LPLV, 20 weeks
- event definition
- Source null
- undenominated note
- Source null
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- quality of life
- setting source links
Preserved source evidence · Not medical advice