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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003540-21 | EudraCT Number |
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The purpose of this study was to confirm the preliminary evidence from early clinical trials that midostaurin may provide clinical benefit not only to AML patients with the FLT3-mutations but also in FLT3-MN (SR<0.05) AML (FLT3 mutant to wild type signal ratio below the 0.05 clinical cut-off).
This study evaluated the efficacy and safety of midostaurin in combination with daunorubicin or idarubicin and cytarabine for induction and intermediate-dose cytarabine for consolidation, and midostaurin single agent post-consolidation therapy in newly diagnosed patients with FLT3-MN (SR<0.05) AML.
This was a multi-center, multinational, randomized, double-blind Phase III study using a group sequential design. Subjects were stratified according to age (<60 vs. ≥ 60 years). Subjects within each stratum were randomized in a 1:1 ratio into one of two treatment arms: Midostaurin + chemotherapy 'or' Placebo + chemotherapy.
The study consisted of the following phases:
Screening/randomization phase: Subjects had to sign informed consent form before screening for enrollment. Subjects started chemotherapy at day 1 and were randomized at day 8.
Induction phase: All subjects received at least one cycle (28 days) of induction therapy with continuous infusion cytarabine (D1 - D7) and daunorubicin or idarubicin (D1 - D3) (induction 1). Subjects who did not achieve CR or CRi with adequate blood count recovery after Induction 1 received a second cycle with intermediate-dose cytarabine (D1 - D3) and daunorubicin or idarubicin (D1 - D3) (induction 2). Subjects who did not achieve CR or CRi with adequate blood recovery after induction 2 discontinued study treatment and were followed for survival.
Consolidation phase: Subjects who achieved CR or CRi with adequate blood count recovery after induction with one or two cycles of induction proceeded to consolidation therapy with either 3 or 4 cycles respectively of intermediate-dose cytarabine (D1 - D3), or to Hematopoietic Stem Cells Transplantation (HSCT) with or without preceding consolidation cycles.
Post-consolidation phase: Subjects who maintained CR or CRi with adequate blood count recovery at the end of the consolidation phase received 12 cycles (28 days/cycle) of continuous therapy with midostaurin or placebo twice daily at 50 mg. Subjects who underwent HSCT after achieving CR or CRi with adequate blood count recovery received midostaurin or placebo twice daily 50 mg post-transplant therapy, continuously, for up to 12 cycles (28 days/cycle). Post HSCT post-consolidation therapy began >30 days but not later than 100 days following HSCT.
Follow-up phase: All enrolled subjects were followed through the treatment period and until relapse/treatment failure, thereafter for start of new line of therapy and survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Midostaurin + chemotherapy | Experimental | Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
| Placebo + chemotherapy | Placebo Comparator | Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midostaurin | Drug | Midostaurin was provided as 25 mg capsules 8PC, was supplied as double-blind in blister packs and taken orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event Free Survival (EFS) | EFS was defined as the time from randomization to failure to obtain a complete remission (CR) or Complete remission with incomplete hematologic recovery (CRi) with adequate blood count recovery in induction, relapse after CR or CRi with adequate blood count recovery or death due to any cause, whichever occurred first as assessed by the investigator. | From date of Randomization up to approx. 30 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) (Key Secondary) | OS was defined as the time from randomization to date of death due to any cause. Patients entered the survival follow-up phase once they completed the safety follow up period (30 days after the last dose of midostaurin/placebo) in case of induction failure or if they had relapsed during post-treatment follow-up. Patients were then contacted by telephone every 3 months +/- 2 weeks or had a visit to follow up on their survival status, per Kaplan-Meier estimates. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Medical Center . | Chicago | Illinois | 60637 | United States | ||
| Dana Farber Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41432755 | Derived | Sechaud R, Peters T, Gu H, Rahmanzadeh G, Sharma GK, Guichard N, Menssen HD. Pharmacogenomic, pharmacokinetic, and safety analysis of CYP3A4/CYP3A5 polymorphisms of midostaurin in patients with acute myeloid leukemia. Eur J Clin Pharmacol. 2025 Dec 23;82(1):19. doi: 10.1007/s00228-025-03971-y. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novctrd.com | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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Participants had to sign informed consent form before screening for enrollment. Participants started chemotherapy at day 1 and were randomized at day 8.
Five hundred and three participants were randomized. However, 2 patients were randomized by error and got discontinued right after randomization. Therefore, the data analysis was considered for 501 participants only (250 participants in midostaurin arm and 251 participants in placebo arm).
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| ID | Title | Description |
|---|---|---|
| FG000 | Midostaurin + Chemotherapy | Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 8, 2018 | Feb 11, 2022 |
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| Placebo | Drug | Placebo was provided as 25 mg soft gelatin capsules 8PC, was supplied as double-blind in blister packs and taken orally. |
|
| Chemotherapy | Drug | Along with the study drug/placebo, chemotherapy was given as well: either Daunorubicin or Idarubicin and Cytarabine - all taken by i.v. |
|
| Between randomization to date of death up to approx. 30 months |
| Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematological Recovery (CRi) But With Adequate Blood Count Recovery Rate. | Assessment was based on the International Working Group (IWG) criteria for AML as per investigator assessment. CR: Bone marrow: < 5% blasts no blasts with Auer rods; Peripheral blood: neutrophils ≥ 1.0 x 109/L platelets ≥ 100 x 109/L, no blasts; No evidence of extramedullary disease (such as central nervous system (CNS) or soft tissue involvement); Transfusion independent. CRi with adequate blood count recovery is defined as the following: Bone marrow < 5% blasts no blasts with Auer rods Peripheral blood Neutrophils >= 1.0 x 109/L and 50 x 109/L <=platelets < 100 x 109/L no blasts No evidence of extramedullary disease (such as CNS or soft tissue involvement). | At maximum 93 days from induction therapy start |
| Percentage of Participants With Minimal Residual Disease (MRD) Negative Status | MRD- rate was defined as the rate of participants reaching MRD at any timepoint. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment. | from start of treatment up to end of post-consolidation (approximately 17 months) |
| Percentage of Participants With Minimal Residual Disease (MRD) Negative Status During Post-consolidation Phase | MRD- rate was defined as the rate of participants reaching MRD at any timepoint during Post-consolidation phase. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment. | from start of post-consolidation to end of post-consolidation phase (up to 12 months) |
| Time to Measurable Residual Disease (MRD) Negativity by Flow Cytometry | Time to MRD- is defined as time from randomization to first occurrence of MRD-. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment. | From date of Randomization up to approx. 17 months |
| Disease-free Survival (DFS) | DFS as measured from the date of first CR or CRi with adequate blood count recovery to relapse or death due to any cause, whichever occurred first. Participants who did not relapse nor die were censored at the last adequate response assessment. Assessment was based on the IWG criteria for AML as per investigator assessment | From date of CR or CRi with adequate blood count recovery up to approx. 30 months |
| Cumulative Incidence of Relapse (CIR) | Cumulative Incidence of Relapse (CIR) was defined for participants with CR or CRi with adequate blood count recovery and was the time from achieving the CR or CRi with adequate blood count recovery until the onset of relapse from CR or CRi with adequate blood recovery. Participants without relapse were censored at the last adequate response assessment. Participants who died without relapse were counted as a competing cause of failure. | From date of CR or CRi with adequate blood count recovery up to approx. 30 months |
| Cumulative Incidence of Death (CID) | Cumulative Incidence of Death (CID) was defined for all participants achieving CR or CRi with adequate blood count recovery measured from the date of achievement of CR or CRi until the date of death due to any reason. Participants not known to have died were censored on the last contact date. Participants who experienced relapse were counted as a competing cause of failure. | From date of CR or CRi with adequate blood count recovery up to approx. 30 months |
| Time to CR or CRi With Adequate Blood Count Recovery | Time to CR or CRi with adequate blood count recovery was defined as the time from randomization to CR or CRi with adequate blood count recovery whichever occurred first | At maximum 93 days from induction therapy start |
| Time to Partial and Full Neutrophil Recovery | The time to neutrophil recovery was assessed for the following criteria: Partial neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥0.5 x 10^9/L. Full neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥1.0 x 10^9/L | At maximum 93 days from induction therapy start |
| Time to Partial and Full Platelet Recovery | Time to platelet recovery was assessed for the following criteria: Partial platelet recovery: Number of days from start of treatment to the first day platelets ≥50 x 10^9/L. Full platelet recovery: Number of days from start of treatment to the first day platelets ≥100 x 10^9/L. | At maximum 93 days from induction therapy start |
| Plasma Concentrations for Midostaurin and Its Metabolites: CGP52421 and CGP62221 for Non-poor Metabolizers | Serial pharmacokinetics (PK) samples were collected in Non-poor metabolizer participants to assess the plasma concentrations of midostaurin, CGP52421 and CGP62221. | from Induction (IND) phase 0hr (predose) to Post-consolidation phase (POSTCONS) 12hr |
| AUC0-t: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The AUC from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). Note: as the last sampling time was at 12 h, AUC0-12h was determined after the first dose, reported at Cycle 1, Day 8 | 0 - 12 hrs |
| AUClast: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The AUC from time zero to the last measurable concentration sampling time after the first dose reported at Cycle 1, Day 8 | 0 - 12 hrs |
| Cmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The maximum (peak) observed plasma drug concentration after the first dose administration reported at Cycle 1, Day 8 | 0 - 12 hrs |
| Tmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration reported at Cycle 1, Day 8 | 0 - 12 hrs |
| Total Score for Each Time Point for the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) | The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better health-related quality of life ( HRQoL). Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. | From date of Randomization up to approx. 18 months |
| Scores for Each Time Point for the EQ5D-5L (a Visual Analogue Scale (VAS)) | The EQ5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient is asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a Visual Analogue Scale (VAS), where the patient is asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state. | From date of Randomization up to approx. 18 months |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Oregon Health and Science Univ | Portland | Oregon | 97239 | United States |
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| FG001 | Placebo + Chemotherapy | Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
| Treated With Midostaurin/Placebo |
|
| Entered Induction Phase |
|
| Entered Consolidation Phase |
|
| Entered Post-Consolidation Phase |
|
| COMPLETED | Completed entire study treatment as per protocol - defined as completion of induction, consolidation and post-consolidation treatment phases |
|
| NOT COMPLETED |
|
|
Full analysis set (FAS) comprised all participants to whom study drug was assigned by randomization.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Midostaurin + Chemotherapy | Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
| BG001 | Placebo + Chemotherapy | Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| ECOG performance status | ECOG performance status determines the ability of a patient to tolerate therapies in serious illness, specifically for chemotherapy. | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Event Free Survival (EFS) | EFS was defined as the time from randomization to failure to obtain a complete remission (CR) or Complete remission with incomplete hematologic recovery (CRi) with adequate blood count recovery in induction, relapse after CR or CRi with adequate blood count recovery or death due to any cause, whichever occurred first as assessed by the investigator. | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Median | 95% Confidence Interval | Months | From date of Randomization up to approx. 30 months |
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| Secondary | Overall Survival (OS) (Key Secondary) | OS was defined as the time from randomization to date of death due to any cause. Patients entered the survival follow-up phase once they completed the safety follow up period (30 days after the last dose of midostaurin/placebo) in case of induction failure or if they had relapsed during post-treatment follow-up. Patients were then contacted by telephone every 3 months +/- 2 weeks or had a visit to follow up on their survival status, per Kaplan-Meier estimates. | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Median | 95% Confidence Interval | Months | Between randomization to date of death up to approx. 30 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematological Recovery (CRi) But With Adequate Blood Count Recovery Rate. | Assessment was based on the International Working Group (IWG) criteria for AML as per investigator assessment. CR: Bone marrow: < 5% blasts no blasts with Auer rods; Peripheral blood: neutrophils ≥ 1.0 x 109/L platelets ≥ 100 x 109/L, no blasts; No evidence of extramedullary disease (such as central nervous system (CNS) or soft tissue involvement); Transfusion independent. CRi with adequate blood count recovery is defined as the following: Bone marrow < 5% blasts no blasts with Auer rods Peripheral blood Neutrophils >= 1.0 x 109/L and 50 x 109/L <=platelets < 100 x 109/L no blasts No evidence of extramedullary disease (such as CNS or soft tissue involvement). | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Number | 95% Confidence Interval | Percentage of participants | At maximum 93 days from induction therapy start |
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| Secondary | Percentage of Participants With Minimal Residual Disease (MRD) Negative Status | MRD- rate was defined as the rate of participants reaching MRD at any timepoint. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment. | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Number | Percentage of participants | from start of treatment up to end of post-consolidation (approximately 17 months) |
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| Secondary | Percentage of Participants With Minimal Residual Disease (MRD) Negative Status During Post-consolidation Phase | MRD- rate was defined as the rate of participants reaching MRD at any timepoint during Post-consolidation phase. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment. | Full analysis in post-consolidation phase comprised of participants who entered post-consolidation phase | Posted | Number | Percentage of participants | from start of post-consolidation to end of post-consolidation phase (up to 12 months) |
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| Secondary | Time to Measurable Residual Disease (MRD) Negativity by Flow Cytometry | Time to MRD- is defined as time from randomization to first occurrence of MRD-. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP). MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment. | Analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Median | 95% Confidence Interval | Days | From date of Randomization up to approx. 17 months |
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| Secondary | Disease-free Survival (DFS) | DFS as measured from the date of first CR or CRi with adequate blood count recovery to relapse or death due to any cause, whichever occurred first. Participants who did not relapse nor die were censored at the last adequate response assessment. Assessment was based on the IWG criteria for AML as per investigator assessment | Full analysis set comprised all participants to whom study drug was assigned by randomization. DFW was derived only for participants who reached CR or CRi with adequate blood count recovery in induction (during first 93 days). | Posted | Median | 95% Confidence Interval | Months | From date of CR or CRi with adequate blood count recovery up to approx. 30 months |
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| Secondary | Cumulative Incidence of Relapse (CIR) | Cumulative Incidence of Relapse (CIR) was defined for participants with CR or CRi with adequate blood count recovery and was the time from achieving the CR or CRi with adequate blood count recovery until the onset of relapse from CR or CRi with adequate blood recovery. Participants without relapse were censored at the last adequate response assessment. Participants who died without relapse were counted as a competing cause of failure. | Full analysis set comprised all participants to whom study drug was assigned by randomization. CIR was only for participants who achieved CR or CRi with adequate blood count recovery. | Posted | Median | 95% Confidence Interval | Months | From date of CR or CRi with adequate blood count recovery up to approx. 30 months |
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| Secondary | Cumulative Incidence of Death (CID) | Cumulative Incidence of Death (CID) was defined for all participants achieving CR or CRi with adequate blood count recovery measured from the date of achievement of CR or CRi until the date of death due to any reason. Participants not known to have died were censored on the last contact date. Participants who experienced relapse were counted as a competing cause of failure. | Full analysis set comprised all participants to whom study drug was assigned by randomization. CID was only for participants who achieved CR or CRi with adequate blood count recovery. | Posted | Median | 95% Confidence Interval | Months | From date of CR or CRi with adequate blood count recovery up to approx. 30 months |
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| Secondary | Time to CR or CRi With Adequate Blood Count Recovery | Time to CR or CRi with adequate blood count recovery was defined as the time from randomization to CR or CRi with adequate blood count recovery whichever occurred first | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Median | 95% Confidence Interval | Days | At maximum 93 days from induction therapy start |
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| Secondary | Time to Partial and Full Neutrophil Recovery | The time to neutrophil recovery was assessed for the following criteria: Partial neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥0.5 x 10^9/L. Full neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥1.0 x 10^9/L | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Median | 95% Confidence Interval | Months | At maximum 93 days from induction therapy start |
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| Secondary | Time to Partial and Full Platelet Recovery | Time to platelet recovery was assessed for the following criteria: Partial platelet recovery: Number of days from start of treatment to the first day platelets ≥50 x 10^9/L. Full platelet recovery: Number of days from start of treatment to the first day platelets ≥100 x 10^9/L. | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Median | 95% Confidence Interval | Months | At maximum 93 days from induction therapy start |
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| Secondary | Plasma Concentrations for Midostaurin and Its Metabolites: CGP52421 and CGP62221 for Non-poor Metabolizers | Serial pharmacokinetics (PK) samples were collected in Non-poor metabolizer participants to assess the plasma concentrations of midostaurin, CGP52421 and CGP62221. | Pharmacokinetic analysis set-all (PAS-all) included all participants in the safety set who provided at least one evaluable PK concentration for Non-poor metabolizers. PK samples were not collected in all timepoints of all patients and reported for Non-poor metabolizers only. | Posted | Mean | Standard Deviation | hour (hr) | from Induction (IND) phase 0hr (predose) to Post-consolidation phase (POSTCONS) 12hr |
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| Secondary | AUC0-t: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The AUC from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). Note: as the last sampling time was at 12 h, AUC0-12h was determined after the first dose, reported at Cycle 1, Day 8 | Pharmacokinetic analysis set-all (PAS-all) included all participants in the safety set who provided at least one evaluable PK concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 0 - 12 hrs |
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| Secondary | AUClast: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The AUC from time zero to the last measurable concentration sampling time after the first dose reported at Cycle 1, Day 8 | Pharmacokinetic analysis set-all (PAS-all) included all participants in the safety set who provided at least one evaluable PK concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/mL | 0 - 12 hrs |
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| Secondary | Cmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The maximum (peak) observed plasma drug concentration after the first dose administration reported at Cycle 1, Day 8 | Pharmacokinetic analysis set-all (PAS-all) included all participants in the safety set who provided at least one evaluable PK concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 - 12 hrs |
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| Secondary | Tmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration reported at Cycle 1, Day 8 | Pharmacokinetic analysis set-all (PAS-all) included all participants in the safety set who provided at least one evaluable PK concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour (hr) | 0 - 12 hrs |
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| Secondary | Total Score for Each Time Point for the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) | The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better health-related quality of life ( HRQoL). Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Mean | Standard Deviation | Scores on a scale | From date of Randomization up to approx. 18 months |
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| Secondary | Scores for Each Time Point for the EQ5D-5L (a Visual Analogue Scale (VAS)) | The EQ5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient is asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a Visual Analogue Scale (VAS), where the patient is asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state. | Full analysis set comprised all participants to whom study drug was assigned by randomization. | Posted | Mean | Standard Deviation | Scores on a scale | From date of Randomization up to approx. 18 months |
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| Post-Hoc | All Collected Deaths | On-treatment deaths were collected from start of treatment (FPFT) up to 30 days after study drug discontinuation, for a maximum duration of approx. 18 months. Randomized but not treated deaths were collected after randomization but before treatment with study drug. Post-treatment survival follow-up deaths were collected after the on-treatment period up to approx. 18 months. Participants who did not die during the on-treatment period and had not stopped study participation at the time of data cut-off (when study was terminated) were censored. | Clinical Database Population: all enrolled participants | Posted | Count of Participants | Participants | Start of study treatment up to 30 days post-treatment for approx. 1 year, prior to study treatment up to LPLV, approx. 18 months |
|
AEs were reported from 1st dose of study treatment until end of treatment plus 30 days, up to a maximum (max.) duration of 573 days (543 days max. exposure plus 30 days post-treatment) for midostaurin and up to a max. duration of 416 days (386 days max. exp. plus 30 days post-treatment) for placebo. Deaths - collected in the post-treatment survival follow-up period from 31 days after last dose of study medication until the end of the study, up to approx. 18 months. These are not considered AEs.
Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post-treatment survival follow-up are not considered Adverse Events. The total number at risk in the post-treatment survival includes patients that entered the post-treatment survival follow-up period.
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 | Midostaurin + Chemotherapy (On-treatment) | AEs during on-treatment period (up to 30 days post-treatment) | 25 | 245 | 95 | 245 | 242 | 245 |
| EG001 | Placebo + Chemotherapy (On-treatment) | AEs during on-treatment period (up to 30 days post-treatment) | 21 | 249 | 114 | 249 | 245 | 249 |
| EG002 | Midostaurin + Chemotherapy (Post-treatment Survival Follow-up) | Deaths collected in the post- treatment survival follow-up phase (starting from day 31 post- treatment). No AEs were collected during this period | 21 | 220 | 0 | 0 | 0 | 0 |
| EG003 | Placebo + Chemotherapy (Post-treatment Survival Follow-up) | Deaths collected in the post- treatment survival follow-up phase (starting from day 31 post- treatment). No AEs were collected during this period | 32 | 228 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Aplastic anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Myocarditis | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Right ventricular dysfunction | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Aplasia | Congenital, familial and genetic disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Thyrotoxic crisis | Endocrine disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Diverticular perforation | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Jejunal stenosis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Mechanical ileus | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Neutropenic colitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Tongue haematoma | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Ulcerative duodenitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Biliary fistula | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Liver disorder | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Acute graft versus host disease | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Graft versus host disease in gastrointestinal tract | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Haemophagocytic lymphohistiocytosis | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Abdominal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Abscess neck | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Acinetobacter infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Anal abscess | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Aspergillus infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Cerebral fungal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Clostridial sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Coronavirus infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Cytomegalovirus colitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Enterococcal sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Gastroenteritis clostridial | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| H1N1 influenza | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Hepatosplenic candidiasis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Klebsiella sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pelvic abscess | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pharyngeal abscess | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pneumonia viral | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pseudomonal sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pulmonary sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Respiratory syncytial virus infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Streptococcal sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Systemic candida | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Systemic mycosis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Viral myocarditis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Expired product administered | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Subdural haemorrhage | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Eastern Cooperative Oncology Group performance status worsened | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Lymphocyte count increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Pulmonary function test decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Chondrocalcinosis pyrophosphate | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cytarabine syndrome | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Chloroma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
| |
| Transitional cell carcinoma recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
| |
| Carotid artery stenosis | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Facial paresis | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Facial spasm | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Myelopathy | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pulmonary toxicity | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypersensitivity vasculitis | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Neutropenic colitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 11, 2021 | Feb 11, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D018365 | Neoplasm, Residual |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C059539 | midostaurin |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
| Male |
|
| Black or African American |
|
| Asian |
|
| Multiple |
|
| Missing |
|
| 1 (Symptomatic, fully ambulatory) |
|
| 2 (Symptomatic, in bed <50% of the day) |
|
| 3 (Symptomatic, in bed >50% of the day) |
|
| Missing |
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.
|
|
|
| OG001 | Placebo + Chemotherapy | Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
|
| Placebo + Chemotherapy |
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.
|
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.
|
|
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
|
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.
|
|
|
|
|
|
|
|
|
|
|
| OG002 | CGP62221 | Active Midostaurin metabolite |
|
|
| CGP62221 |
Active Midostaurin metabolite |
|
|
Active Midostaurin metabolite |
|
|
Active Midostaurin metabolite
|
|
Active Midostaurin metabolite |
|
|
|
|
| OG001 |
| Placebo + Chemotherapy |
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
|
Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation. |
|
|