Trial · NCT00866281
A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
NCT00866281, Phase 1, Phase 2, Terminated, Novartis Pharmaceuticals; results first posted 2015-12-22
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia. Trials, record NCT00866281. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00866281
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
- NCT number
- NCT00866281
- Status
- Terminated
- Phases
- Phase 1, Phase 2
- Enrollment
- 22 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
- Interventions
- midostaurin
- First posted
- 2009-03-20
- Last updated
- 2015-12-22
- Other registries' IDs
- eudract:2008-006931-11
- Results first posted
- 2015-12-22
- Limitations and caveats
- The study was terminated early since despite considerable efforts to boost recruitment, no new participants were enrolled in the final year of this study.
Source ClinicalTrials.gov
Registered outcomes6
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT | Baseline, End of dose escalation phase (6 months) | 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). |
| Secondary | Percentage of Participants With Best Overall Response by Indication | 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) | 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, |
| Secondary | Time to Response With Midostaurin | Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first) | 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. |
| Secondary | Overall Survival With Midostaurin | Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first) | 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. |
| Secondary | Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221 | Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3) | 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. |
| Secondary | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs or SAEs and Death During the Study | Baseline (start of study treatment) up to End of treatment (up to 24 months after last dose or until death whichever occurred first) | 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. |
Source ClinicalTrials.gov
Outcomes6
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT | Baseline, End of dose escalation phase (6 months) | The analysis was performed in dose determining set (DDS) population. Here, 'n' signifies the number of evaluable participants for this measure. | probability estimates | MEAN |
| SECONDARY | Percentage of Participants With Best Overall Response by Indication | 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) | The analysis was performed in full analysis set (FAS) population, defined as all participants to whom study treatment was assigned. | Percentage of Participants | NUMBER |
| SECONDARY | Time to Response With Midostaurin | Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first) | The analysis was performed in FAS population. Here, Number of participants analysed signifies number of responders at specified time points for each arm, respectively. | Days | MEDIAN |
| SECONDARY | Overall Survival With Midostaurin | Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first) | The analysis was performed in FAS population. | Months | MEDIAN |
| SECONDARY | Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221 | Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3) | 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. | nanograms/milliliters (ng/mL) | MEAN |
| SECONDARY | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs or SAEs and Death During the Study | Baseline (start of study treatment) up to End of treatment (up to 24 months after last dose or until death whichever occurred first) | The analysis was performed in safety set population, defined as the participants who received at least one dose of midostaurin. | Participants | NUMBER |
Source ClinicalTrials.gov
Results by group90
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | Younger stratum (≥ 3months -≤ 2 years): (n=2, 5) | 0.03 | 97.5% Confidence Interval 0 to 0.16 | probability estimates |
| Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT | Cohort 2: Midostaurin (60 mg/m^2) | Younger stratum (≥ 3months -≤ 2 years): (n=2, 5) | 0.10 | 97.5% Confidence Interval 0.01 to 0.33 | probability estimates |
| Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | Older stratum (>2 years- <18years): (n=4,6) | 0.03 | 97.5% Confidence Interval 0 to 0.13 | probability estimates |
| Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT | Cohort 2: Midostaurin (60 mg/m^2) | Older stratum (>2 years- <18years): (n=4,6) | 0.08 | 97.5% Confidence Interval 0.01 to 0.26 | probability estimates |
| Percentage of Participants With Best Overall Response by Indication | AML Subjects | Leukemia free state | 0 | Percentage of Participants | |
| Percentage of Participants With Best Overall Response by Indication | MLLr-ALL Subjects | Leukemia free state | 0 | Percentage of Participants | |
| Percentage of Participants With Best Overall Response by Indication | AML Subjects | Morphological complete remission | 0 | Percentage of Participants | |
| Percentage of Participants With Best Overall Response by Indication | MLLr-ALL Subjects | Morphological complete remission | 0 | Percentage of Participants | |
| Percentage of Participants With Best Overall Response by Indication | AML Subjects | Incomplete morphological complete remission | 11.1 | Percentage of Participants | |
| Percentage of Participants With Best Overall Response by Indication | MLLr-ALL Subjects | Incomplete morphological complete remission | 0 | Percentage of Participants |
1 to 10 of 90Source ClinicalTrials.gov
See all 90 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 7 | |
| Overall Study | STARTED | Cohort 2: Midostaurin (60 mg/m^2) | 15 | |
| Overall Study | COMPLETED | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 0 | |
| Overall Study | COMPLETED | Cohort 2: Midostaurin (60 mg/m^2) | 0 | |
| Overall Study | NOT COMPLETED | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 7 | |
| Overall Study | NOT COMPLETED | Cohort 2: Midostaurin (60 mg/m^2) | 15 |
Source ClinicalTrials.gov
Adverse events274
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 0 | 7 | |
| other | Anaemia | Blood and lymphatic system disorders | Cohort 2: Midostaurin (60 mg/m^2) | 5 | 15 | |
| other | Febrile Neutropenia | Blood and lymphatic system disorders | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 0 | 7 | |
| other | Febrile Neutropenia | Blood and lymphatic system disorders | Cohort 2: Midostaurin (60 mg/m^2) | 1 | 15 | |
| other | Leukopenia | Blood and lymphatic system disorders | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 0 | 7 | |
| other | Leukopenia | Blood and lymphatic system disorders | Cohort 2: Midostaurin (60 mg/m^2) | 1 | 15 | |
| other | Lymphopenia | Blood and lymphatic system disorders | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 0 | 7 | |
| other | Lymphopenia | Blood and lymphatic system disorders | Cohort 2: Midostaurin (60 mg/m^2) | 2 | 15 | |
| other | Neutropenia | Blood and lymphatic system disorders | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 0 | 7 | |
| other | Neutropenia | Blood and lymphatic system disorders | Cohort 2: Midostaurin (60 mg/m^2) | 3 | 15 |
1 to 10 of 274Source ClinicalTrials.gov
See all 274 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | ||
| Total, all-cause mortality | Cohort 2: Midostaurin (60 mg/m^2) | ||
| Total, other adverse events | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 6 | 7 |
| Total, other adverse events | Cohort 2: Midostaurin (60 mg/m^2) | 15 | 15 |
| Total, serious adverse events | Cohort 1: Midostaurin (30 Milligrams/Meters^2) | 3 | 7 |
| Total, serious adverse events | Cohort 2: Midostaurin (60 mg/m^2) | 6 | 15 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons1
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison |
|---|
| Cohort 1: Midostaurin (30 Milligrams/Meters^2) vs Cohort 2: Midostaurin (60 mg/m^2): serious adverse events |
Source Trial comparisons
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT00866281
GET https://conductscience.org/api/trials/v1/NCT00866281/results?page=2