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This study evaluated the efficacy and safety of midostaurin in combination with daunorubicin/cytarabine induction, high dose cytarabine consolidation and midostaurin single agent continuation therapy in newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML).
This was a Phase II, multi-center trial consisting of two parts; Part 1: an open label, safety evaluation part in Japan only (minimum of three evaluable subjects) and Part 2: a double-blind, randomized, placebo-controlled part (60 subjects). Part 1 in Japan and Part 2 outside Japan were initiated simultaneously. Part 1 was conducted to evaluate the safety and tolerability of midostaurin in combination with daunorubicin/cytarabine induction and high-dose cytarabine consolidation in Japanese subjects and was a pre-requisite before allowing participation of Japan in Part 2. Data from Part 1 was reviewed by an Independent safety Committee (ISC) designated by the Sponsor. The ISC reviewed all available safety data in subjects from Japan up to the time of the safety review data cut-off date (6-Sep-2018). A meeting with the ISC was held on 25-Sep-2018: based on safety evaluation in three evaluable subjects, the ISC members recommended to start Part 2 in Japan.
Part 2 of the study included screening phase, treatment phase composed of up to 18 cycles of midostaurin/placebo treatment in combination with chemotherapy (daunorubicin and cytarabine) during induction and consolidation and alone during continuation and 30 days safety follow up from last dose of study treatment (daunorubicin or cytarabine or midostaurin/placebo); and follow up phase for continued remission and survival follow-up (until 36 months after Day 1 of the last subject). Subjects who provided written informed consent were screened for eligibility during the period up to 7 days immediately prior to starting chemotherapy (Day 1). The subject was randomized at Day 8 to receive either midostaurin or placebo only if FLT3 status was mutated. Treatment phase included induction, consolidation and continuation therapies.
Induction therapy: All screened subjects started induction therapy with chemotherapy from Day 1 to Day 7, while the FLT3 mutation status was being determined. Subjects who achieved CR already with induction Cycle 1 went directly to consolidation therapy without a second cycle of induction therapy. Subjects who did not achieve CR with one cycle of induction received a second induction cycle with same treatment as in Cycle 1. Subjects who did not achieve CR after induction 2 discontinued the study treatment and were followed in safety follow up and survival follow-up.
Consolidation therapy: Subjects who achieved a CR after 1 or 2 cycles of induction received consolidation therapy with 3 cycles of high-dose cytarabine for the Japan Adult Leukemia Study Group (JALSG) regimen and 4 cycles of high-dose cytarabine as tolerated for the Randomized AML Trial In FLT3+ subjects <60 Years old (RATIFY) regimen. Subjects received midostaurin/placebo, orally twice a day, on Days 8 to 21 of each cycle. Each consolidation cycle began within two weeks following hematopoietic recovery (ANC ≥ 1.0 x 109/L, platelet count ≥ 100 x 109/L) but no sooner than four weeks from the beginning of the previous cycle.
Continuation therapy: After hematopoietic recovery (ANC ≥ 1.0 x 109/L, platelet count ≥ 100 x 109/L) following the final cycle of consolidation but no sooner than 14 days after the last dose of midostaurin/placebo during the last consolidation cycle, subjects who maintained a CR received up to 12 cycles (28 days/cycle) of continuous therapy with midostaurin or placebo twice a day. Safety was assessed in this treatment phase for each subject until 30 days after the end of treatment (EOT) and included routine safety monitoring.
The follow-up phases included post treatment follow-up and survival follow-up. During post-treatment follow-up, all subjects continued to be assessed for relapse i.e. every 2 months during years 1 and 2, every 3 months on year 3 and 4 and then yearly and at time of relapse until relapse, withdrawal of consent, death, loss to follow up, or end of study, whichever was earlier following the end of study treatment for any reason other than persistent AML. Subjects who discontinued study treatment due to persistent AML or relapse and the post treatment follow-up phase due to relapse entered a survival follow-up period during which survival was recorded every 3 months. Survival information was obtained by clinical visits or telephone calls or other means until death, withdrawal of consent, lost to follow-up or end of study, whichever was earlier.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Midostaurin | Experimental | Patients took study drug on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase. |
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| Placebo | Placebo Comparator | Patients took placebo on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midostaurin | Drug | Midostaurin 50 mg [two 25 mg capsules] were administered twice per day by mouth on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Safety Events (Part 1, Japan Only) | Percentage of Safety Events, defined as death or serious adverse event leading to treatment discontinuation that occurs on or before Day 21 of the first Consolidation cycle. This was determined by the Independent Safety Committee (ISC) to be definitely or probably related to midostaurin. Percentage was calculated based on the percentage of subjects with safety event out of 3 evaluable subjects in Part 1. | up to Day 21 of the first Consolidation cycle; cycle = 28 days |
| Event Free Survival (EFS) (Part 2 - Randomized, Controlled) | Event Free survival is defined as the time from the date of randomization until an EFS event is observed. An EFS event is defined as a failure to obtain a complete remission (CR) within an induction 2, relapse after CR, or death due to any cause, whichever occurs first. The objective was to evaluate the efficacy based on EFS of midostaurin versus placebo in combination with daunorubicin/cytarabine induction, with high-dose cytarabine consolidation, and with midostaurin single agent continuation therapy in newly diagnosed patients with FLT3-mutated AML. | up to 3 years after last patient started treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Overall survival defined as the time from the date of randomization to date of death due to any cause | up to 3 years after last patient started treatment |
| Percentage of Participants With Complete Remission (CR) |
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Inclusion Criteria:
Diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL (acute promyelocytic leukemia) with PML-RARA are not eligible
Documented presence of an ITD and/or TKD activating mutation in the FLT3 gene, as determined by analysis in a Novartis designated laboratory An exception will be patients who are enrolled into the part 1 in Japan, who may be treated with midostaurin irrespective of AML FLT3 genotype.
Patients must meet the following laboratory value criteria that indicate adequate organ function at the screening visit:
Suitability for intensive chemotherapy in the judgment of the investigator
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Pokfulam | Hong Kong | ||||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Subjects were enrolled in 6 countries and at 34 study centers. In Part 1, subjects started chemotherapy at day 1 and midostaurin at day 8. In Part 2, subjects started chemotherapy at day 1 and were randomized to midostaurin or placebo at day 8.
Part 1 of the study enrolled 5 Japan adult subjects with newly diagnosed (ND) FLT3-mutated or non-mutated AML. Part 2 randomized 62 adult subjects with ND FLT3-mutated AML. The efficacy analysis was on the 62 randomized subjects in Part 2. The safety analysis was considered separately on 5 subjects in Part 1 & 61 out of 62 randomized subjects in Part 2, as 1 subject did not receive randomized treatment (placebo). The PK analysis was on subjects treated with midostaurin in Part 1 or Part 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Midostaurin: Part 1 (Japan Only) | Part 1 was conducted to evaluate the safety and tolerability of midostaurin in combination with daunorubicin/cytarabine induction and high-dose cytarabine consolidation in Japanese patients. The safety evaluation period began on Day 1 of the first induction cycle (Cycle 1 Day 1) and continued until Day 21 of the first consolidation cycle. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 - Safety Evaluation |
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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 | Sep 10, 2020 | Oct 5, 2023 |
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| Placebo | Drug | Placebo, two capsules, were administered twice per day by mouth on day 8-21 during induction and consolidation phase; then on days 1-28 for 12 cycles in the continuation (post consolidation) phase. |
|
Complete Remission is defined as the percentage of participants with a CR according to Chelson Criteria, at various timepoints
| up to 3 years after last patient started treatment |
| Percentage of Participants With Cumulative Incidence of Relapse (CIR) | CIR (only for patients who achieved CR after study treatment initiation), is measured from the date of first CR to relapse or death due to AML, whichever occurs first. | up to 3 years after last patient started treatment |
| Pharmakinetics (PK) for Midostaurin: AUClast & AUC0-t | Evaluate AUClast & AUC0-t PK parameters for midostaurin. AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUC0-t: The area under the curve (AUC) from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). | Induction Phase: Pre-dose and 1, 3, 6 and 12 hours post dose in Cycle 1 Day 8 |
| Pharmakinetics (PK) for Midostaurin: Cmax | Evaluate Cmax parameter for midostaurin. Cmax: The maximum (peak) observed plasma drug concentration after the first dose administration of midostaurin (mass x volume-1). | Induction Phase: Pre-dose and 1, 3, 6 and 12 hours post dose in Cycle 1 Day 8 |
| Metabolite CGP52421: PK Parameters AUClast, AUC0-t | Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421. AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUC0-t: The area under the curve (AUC) from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). | Induction Phase: Cycle 1 Day 8 |
| Metabolite CGP52421: PK Parameter Cmax | Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421: Cmax. Cmax: The maximum (peak) observed plasma drug concentration after the first dose administration of midostaurin (mass x volume-1). | Induction Phase: Cycle 1 Day 8 |
| Metabolite CGP62221: PK Parameters: AUClast, AUC0-t | Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221 PK parameters AUClast, AUC0-t | Induction Phase: Cycle 1 Day 8 |
| Metabolite CGP62221: PK Parameter: Cmax | Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221 PK parameter Cmax. Cmax: The maximum (peak) observed plasma drug concentration after the first dose administration of midostaurin (mass x volume-1). | Induction Phase: Cycle 1 Day 8 |
| Change From Baseline in Quality of Life (QoL) Per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | The EORTC QLQ-C30 is a 30-item questionnaire with multi-item scales and single-item measures, including five functional scales (physical, role, emotional, cognitive, and social), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact), and a global health status/QoL scale. Scores range from 0 to 100, with higher scores indicating higher response levels. High functional scale scores denote healthy functioning, high global QoL scores indicate high QoL, and high symptom scores reflect high symptom levels. Scoring follows the EORTC Scoring Manual, reported by absolute change from baseline. EOI = End of Induction; EOCons = End of Consolidation; EOCont = End of Continuation; EOT = End of Treatment. | EOI: up to 1.84 months (after 2 cycles); EOCons: up to 5.52 months (after 4 cycles); EOCont: up to 16.56 months (after 12 cycles); EOT: up to 16.56 months maximum, depending on treatment duration; each cycle = 28 days |
| Quality of Life (QoL) Per Patient Global Impression of Change (PGIC) | The PGIC is a single self-reported item that asks about change in status of subject's overall satisfaction with medication since starting the standalone study. The specific wording of the PGIC is "Directions: Circle the one number that best describes how your overall satisfaction with your medication had changed since starting the study": "Very much improved" =1; "Much improved" =2; "Minimally improved" =3; "No change" =4; "Minimally worse" =5; "Much worse" =6; "Very much worse" =7. PGI-C questions have been widely used to assess the patient perspective of improvement in clinical trials and have shown clinical validity in a variety of indications, including depression, urinary incontinence and adult asthma and the PGIC score determined frequencies and percentages by scheduled timepoint. EOI = End of Induction; EOCons = End of Consolidation; EOCont = End of Continuation; EOT = End of Treatment. | EOI: up to 1.84 months (after 2 cycles); EOCons: up to 5.52 months (after 4 cycles); EOCont: up to 16.56 months (after 12 cycles); EOT: up to 16.56 months maximum, depending on treatment duration; each cycle = 28 days |
| Nagoya |
| Aichi-ken |
| 466-8650 |
| Japan |
| Novartis Investigative Site | Toyoake | Aichi-ken | 470 1192 | Japan |
| Novartis Investigative Site | Kashiwa | Chiba | 277 8577 | Japan |
| Novartis Investigative Site | Fukuoka | Fukuoka | 812-8582 | Japan |
| Novartis Investigative Site | Fukushima | Fukushima | 960 1295 | Japan |
| Novartis Investigative Site | Sapporo | Hokkaido | 064 0804 | Japan |
| Novartis Investigative Site | Isehara | Kanagawa | 259-1193 | Japan |
| Novartis Investigative Site | Nagasaki | Nagasaki | 852-8501 | Japan |
| Novartis Investigative Site | Okayama | Okayama-ken | 701-1192 | Japan |
| Novartis Investigative Site | Osaka | Osaka | 543-8555 | Japan |
| Novartis Investigative Site | Ōsaka-sayama | Osaka | 589 8511 | Japan |
| Novartis Investigative Site | Hamamatsu | Shizuoka | 432-8580 | Japan |
| Novartis Investigative Site | Shimotsuke | Tochigi | 329-0498 | Japan |
| Novartis Investigative Site | Bunkyo Ku | Tokyo | 113-8677 | Japan |
| Novartis Investigative Site | Bunkyo-ku | Tokyo | 113-8603 | Japan |
| Novartis Investigative Site | Shinagawa Ku | Tokyo | 141 8625 | Japan |
| Novartis Investigative Site | Aomori | 030 8553 | Japan |
| Novartis Investigative Site | Fukuoka | 810-8563 | Japan |
| Novartis Investigative Site | Kochi | 781 8555 | Japan |
| Novartis Investigative Site | Kyoto | 606 8507 | Japan |
| Novartis Investigative Site | Osaka | 534-0021 | Japan |
| Novartis Investigative Site | Yamagata | 990 9585 | Japan |
| Novartis Investigative Site | Moscow | 123182 | Russia |
| Novartis Investigative Site | Moscow | 125284 | Russia |
| Novartis Investigative Site | Saint Petersburg | 197341 | Russia |
| Novartis Investigative Site | Seoul | Seocho Gu | 06591 | South Korea |
| Novartis Investigative Site | Seoul | 03722 | South Korea |
| Novartis Investigative Site | Seoul | 06351 | South Korea |
| Novartis Investigative Site | Putzu City | Chiayi Hsien | 61363 | Taiwan |
| Novartis Investigative Site | Kaohsiung City | 83301 | Taiwan |
| Novartis Investigative Site | Taipei | 10002 | Taiwan |
| Novartis Investigative Site | Taoyuan | 33305 | Taiwan |
| Novartis Investigative Site | Hanoi | 100000 | Vietnam |
| FG001 | Midostaurin: Part 2 | Patients took study drug on day 8-21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. |
| FG002 | Placebo: Part 2 | Patients took Placebo on day 8 - 21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. |
| COMPLETED |
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| NOT COMPLETED |
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| Part 2 - Efficacy |
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Full Analysis Set (FAS): The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. Therefore, all Japanese subjects treated during Part 1 were not eligible for the FAS.
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| ID | Title | Description |
|---|---|---|
| BG000 | Midostaurin: Part 1 (Japan Only) | Part 1 was conducted to evaluate the safety and tolerability of midostaurin in combination with daunorubicin/cytarabine induction and high-dose cytarabine consolidation in Japanese patients. The safety evaluation period began on Day 1 of the first induction cycle (Cycle 1 Day 1) and continued until Day 21 of the first consolidation cycle. |
| BG001 | Midostaurin: Part 2 | Patients took study drug on day 8-21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. |
| BG002 | Placebo: Part 2 | Patients took Placebo on day 8 - 21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | 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 | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Safety Events (Part 1, Japan Only) | Percentage of Safety Events, defined as death or serious adverse event leading to treatment discontinuation that occurs on or before Day 21 of the first Consolidation cycle. This was determined by the Independent Safety Committee (ISC) to be definitely or probably related to midostaurin. Percentage was calculated based on the percentage of subjects with safety event out of 3 evaluable subjects in Part 1. | Patients enrolled in Part 1: 3 patients out of 5 patients in Part 1 were evaluable for safety evaluation as determined by Independent Safety Committee (ISC). | Posted | Number | Participants | up to Day 21 of the first Consolidation cycle; cycle = 28 days |
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| Primary | Event Free Survival (EFS) (Part 2 - Randomized, Controlled) | Event Free survival is defined as the time from the date of randomization until an EFS event is observed. An EFS event is defined as a failure to obtain a complete remission (CR) within an induction 2, relapse after CR, or death due to any cause, whichever occurs first. The objective was to evaluate the efficacy based on EFS of midostaurin versus placebo in combination with daunorubicin/cytarabine induction, with high-dose cytarabine consolidation, and with midostaurin single agent continuation therapy in newly diagnosed patients with FLT3-mutated AML. | Full Analysis Set (FAS): The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. Therefore, all Japanese subjects treated during Part 1 were not eligible for the FAS. | Posted | Median | 95% Confidence Interval | Months | up to 3 years after last patient started treatment |
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| Secondary | Overall Survival | Overall survival defined as the time from the date of randomization to date of death due to any cause | FAS: The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. Therefore, all Japanese subjects treated during Part 1 were not eligible for the FAS. | Posted | Median | 95% Confidence Interval | Months | up to 3 years after last patient started treatment |
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| Secondary | Percentage of Participants With Complete Remission (CR) | Complete Remission is defined as the percentage of participants with a CR according to Chelson Criteria, at various timepoints | FAS: The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. Therefore, all Japanese subjects treated during Part 1 were not eligible for the FAS. | Posted | Number | 95% Confidence Interval | Percentage of participants | up to 3 years after last patient started treatment |
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| Secondary | Percentage of Participants With Cumulative Incidence of Relapse (CIR) | CIR (only for patients who achieved CR after study treatment initiation), is measured from the date of first CR to relapse or death due to AML, whichever occurs first. | FAS: The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. Therefore, all Japanese subjects treated during Part 1 were not eligible for the FAS. This analysis was on FAS but only on participants who had achieved a CR. | Posted | Count of Participants | Participants | up to 3 years after last patient started treatment |
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| Secondary | Pharmakinetics (PK) for Midostaurin: AUClast & AUC0-t | Evaluate AUClast & AUC0-t PK parameters for midostaurin. AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUC0-t: The area under the curve (AUC) from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). | PK analysis set for full PK (PAS-full): The PAS-full included all subjects in the PAS-all, who provide an evaluable PK profile. A profile was considered evaluable if all of the following conditions are satisfied: Subject received the planned dose of midostaurin on C1D8 of induction therapy; Subject did not vomit within 4 hours of the dosing of midostaurin on C1D8 of induction therapy; Subject provided at least one primary PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Induction Phase: Pre-dose and 1, 3, 6 and 12 hours post dose in Cycle 1 Day 8 |
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| Secondary | Pharmakinetics (PK) for Midostaurin: Cmax | Evaluate Cmax parameter for midostaurin. Cmax: The maximum (peak) observed plasma drug concentration after the first dose administration of midostaurin (mass x volume-1). | PAS-full: PK analysis set for full PK (PAS-full): The PAS-full included all subjects in the PAS-all, who provide an evaluable PK profile. A profile was considered evaluable if all of the following conditions are satisfied: Subject received the planned dose of midostaurin on C1D8 of induction therapy; Subject did not vomit within 4 hours of the dosing of midostaurin on C1D8 of induction therapy; Subject provided at least one primary PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Induction Phase: Pre-dose and 1, 3, 6 and 12 hours post dose in Cycle 1 Day 8 |
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| Secondary | Metabolite CGP52421: PK Parameters AUClast, AUC0-t | Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421. AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1) AUC0-t: The area under the curve (AUC) from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). | PAS-full: PK analysis set for full PK (PAS-full): The PAS-full included all subjects in the PAS-all, who provide an evaluable PK profile. A profile was considered evaluable if all of the following conditions are satisfied: Subject received the planned dose of midostaurin on C1D8 of induction therapy; Subject did not vomit within 4 hours of the dosing of midostaurin on C1D8 of induction therapy; Subject provided at least one primary PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Induction Phase: Cycle 1 Day 8 |
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| Secondary | Metabolite CGP52421: PK Parameter Cmax | Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421: Cmax. Cmax: The maximum (peak) observed plasma drug concentration after the first dose administration of midostaurin (mass x volume-1). | PAS-full: PK analysis set for full PK (PAS-full): The PAS-full included all subjects in the PAS-all, who provide an evaluable PK profile. A profile was considered evaluable if all of the following conditions are satisfied: Subject received the planned dose of midostaurin on C1D8 of induction therapy; Subject did not vomit within 4 hours of the dosing of midostaurin on C1D8 of induction therapy; Subject provided at least one primary PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Induction Phase: Cycle 1 Day 8 |
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| Secondary | Metabolite CGP62221: PK Parameters: AUClast, AUC0-t | Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221 PK parameters AUClast, AUC0-t | PAS-full: PK analysis set for full PK (PAS-full): The PAS-full included all subjects in the PAS-all, who provide an evaluable PK profile. A profile was considered evaluable if all of the following conditions are satisfied: Subject received the planned dose of midostaurin on C1D8 of induction therapy; Subject did not vomit within 4 hours of the dosing of midostaurin on C1D8 of induction therapy; Subject provided at least one primary PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Induction Phase: Cycle 1 Day 8 |
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| Secondary | Metabolite CGP62221: PK Parameter: Cmax | Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221 PK parameter Cmax. Cmax: The maximum (peak) observed plasma drug concentration after the first dose administration of midostaurin (mass x volume-1). | PAS-full: PK analysis set for full PK (PAS-full): The PAS-full included all subjects in the PAS-all, who provide an evaluable PK profile. A profile was considered evaluable if all of the following conditions are satisfied: Subject received the planned dose of midostaurin on C1D8 of induction therapy; Subject did not vomit within 4 hours of the dosing of midostaurin on C1D8 of induction therapy; Subject provided at least one primary PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Induction Phase: Cycle 1 Day 8 |
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| Secondary | Change From Baseline in Quality of Life (QoL) Per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | The EORTC QLQ-C30 is a 30-item questionnaire with multi-item scales and single-item measures, including five functional scales (physical, role, emotional, cognitive, and social), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact), and a global health status/QoL scale. Scores range from 0 to 100, with higher scores indicating higher response levels. High functional scale scores denote healthy functioning, high global QoL scores indicate high QoL, and high symptom scores reflect high symptom levels. Scoring follows the EORTC Scoring Manual, reported by absolute change from baseline. EOI = End of Induction; EOCons = End of Consolidation; EOCont = End of Continuation; EOT = End of Treatment. | Participants in the full analysis set (FAS) with an available assessment for the outcome measure at each timepoint. FAS: The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. | Posted | Mean | Standard Deviation | scores on a scale | EOI: up to 1.84 months (after 2 cycles); EOCons: up to 5.52 months (after 4 cycles); EOCont: up to 16.56 months (after 12 cycles); EOT: up to 16.56 months maximum, depending on treatment duration; each cycle = 28 days |
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| Secondary | Quality of Life (QoL) Per Patient Global Impression of Change (PGIC) | The PGIC is a single self-reported item that asks about change in status of subject's overall satisfaction with medication since starting the standalone study. The specific wording of the PGIC is "Directions: Circle the one number that best describes how your overall satisfaction with your medication had changed since starting the study": "Very much improved" =1; "Much improved" =2; "Minimally improved" =3; "No change" =4; "Minimally worse" =5; "Much worse" =6; "Very much worse" =7. PGI-C questions have been widely used to assess the patient perspective of improvement in clinical trials and have shown clinical validity in a variety of indications, including depression, urinary incontinence and adult asthma and the PGIC score determined frequencies and percentages by scheduled timepoint. EOI = End of Induction; EOCons = End of Consolidation; EOCont = End of Continuation; EOT = End of Treatment. | Participants in the full analysis set (FAS) with an available assessment for the outcome measure at each timepoint. FAS: The FAS comprised of all subjects to whom study drug (midostaurin/placebo) had been assigned by randomization. | Posted | Number | Participants | EOI: up to 1.84 months (after 2 cycles); EOCons: up to 5.52 months (after 4 cycles); EOCont: up to 16.56 months (after 12 cycles); EOT: up to 16.56 months maximum, depending on treatment duration; each cycle = 28 days |
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| Post-Hoc | All Collected Deaths | Pre-treatment deaths were collected from screening visit up to the first day of treatment, for a maximum duration of 21 days. Participants who died during the screening period are considered as screen failures. On-treatment deaths were collected from start of treatment (FPFT) up to 30 days after study drug discontinuation, for a maximum duration of approx. 55 months. Post-treatment survival follow-up deaths were collected after the on-treatment period up to approx. 36 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 | No | Start of study treatment up to 30 days post-treatment for approx. 1 year, prior to study treatment (before randomization) up to LPLV, approx. 55 months |
|
Adverse events were collected from first dose of study treatment to 30 days after last dose of study medication (on-treatment), up to approx. 55 months. Deaths were collected in the post-treatment survival follow up from 31 days after last dose of study medication until the end of the study, up to approx. 36 months. These are not considered AEs
An Adverse Event is any sign or symptom occurring during a trial and safety follow-up, excluding deaths in post-treatment survival follow-up. The total at risk includes patients entering post-treatment survival after the 30-day post-treatment period. Death data was reported for all enrolled patients, while Adverse Events data was reported from those receiving at least one dose of the study drug (midostaurin/placebo).
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: Part 1 (Japan Only) (On-treatment) | Part 1 was conducted to evaluate the safety and tolerability of midostaurin in combination with daunorubicin/cytarabine induction and high-dose cytarabine consolidation in Japanese patients. The safety evaluation period began on Day 1 of the first induction cycle (Cycle 1 Day 1) and continued until Day 21 of the first consolidation cycle. | 1 | 5 | 2 | 5 | 5 | 5 |
| EG001 | Midostaurin: Part 2 (On-treatment) | Patients took study drug on day 8-21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. | 3 | 30 | 12 | 30 | 30 | 30 |
| EG002 | Placebo Part 2 (On-treatment) | Patients took Placebo on day 8 - 21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. This group excludes the 1 participant who was randomized to placebo but did not receive placebo and died during the on-treatment period. | 1 | 31 | 10 | 31 | 31 | 31 |
| EG003 | Midostaurin: Part 1 (Japan Only) (Post-treatment Survival Follow-up) | Deaths collected in the post- treatment survival follow-up in Part 1 phase (starting from day 31 post- treatment in Part 1). No AEs were collected during this period. | 2 | 4 | 0 | 0 | 0 | 0 |
| EG004 | Midostaurin: Part 2 (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. | 7 | 27 | 0 | 0 | 0 | 0 |
| EG005 | Placebo: Part 2 (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. | 6 | 30 | 0 | 0 | 0 | 0 |
| EG006 | Other Participants | These participants were not randomized to any treatment but received chemotherapy and died during the study. This group also includes 1 participant who was randomized to placebo but did not receive placebo and died during the on-treatment period. | 7 | 7 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Necrotising colitis | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Escherichia sepsis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Fungaemia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cardiac hypertrophy | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Gastrointestinal mucosal disorder | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Intestinal haemorrhage | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Neutropenic colitis | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Catheter site erythema | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Catheter site cellulitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Cellulitis of male external genital organ | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Ecthyma | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Hepatosplenic candidiasis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
| |
| Allergic transfusion reaction | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Wound complication | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Antithrombin III decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Coagulation test abnormal | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Full blood count increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Immunoglobulins decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Ventilation/perfusion scan abnormal | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Fluid retention | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Head discomfort | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA (25.1) | 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 | Dec 6, 2022 | Oct 5, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C059539 | midostaurin |
Not provided
Not provided
Not provided
| Physician Decision |
|
| Withdrawal by Subject |
|
| Progressive disease |
|
| 60 - <65 years |
|
| ≥65 years |
|
| Male |
|
| Korean |
|
| Chinese |
|
| Vietnamese |
|
| Missing |
|
| White |
|
| Safety events determined by ISC related to midostaurin (n = 3, 0, 0) |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
|
|
|
|
|
| OG001 |
| Placebo: Part 2 |
Patients took Placebo on day 8 - 21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. |
|
|
| OG001 | Placebo: Part 2 | Patients took Placebo on day 8 - 21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. |
|
|
| OG002 | Placebo: Part 2 | Patients took Placebo on day 8 - 21 during induction and consolidation phase, then on days 1-28 for 12 cycles in the continuation (post-consolidation) phase. This group excludes 1 participant who was randomized to placebo but did not receive placebo and died during the on-treatment period. |
| OG003 | Other Participants | These participants were not randomized to any treatment but received chemotherapy and died during the study. This group also includes 1 participant who was randomized to placebo but did not receive placebo and died during the on-treatment period. |
|
|
| Title | Measurements |
|---|---|
|
|
|
|