Acute Myeloid Leukemia
Conditions
Keywords
acute myeloid leukemia, AML, FLT3-ITD, midostaurin, PKC412, allogeneic hematopoeitic stem cell tranplant, SCT, HSCT, CR1, adult
Brief summary
To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem cell transplant,
Interventions
DRUGMidostaurin
Midostaurin was supplied in 25mg soft gelatin capsule taken orally twice a day for 28 days of each cycle. Patients will be treated for 12 cycles.
OTHERStandard of Care
Standard of Care was not defined per protocol. The investigator prescribed based on the commonly used medications given in the post SCT setting.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients between 18 and 70 years of age * Patients with ECOG Performance Status of ≤ 2 * Patients with a documented unequivocal diagnosis of AML according to WHO 2008 classification (\>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia). * Patients with a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation) * Patients who undersent allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria had to be met: HLA typing to include available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single allelic mismatch allowed * Patients who had received a conditioning regimen which included one of the following: Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Fludarabine (120-180 mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2) Melphalan (≤ 150 mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI) Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy) • Recovery of counts by day 42 and was able to start midostaurin by day 60 post-HSCT (first dose of midostaurin to start no earlier than 28 days post-HSCT); ANC \>1000µL, platelets ≥20,000 without platelet transfusion
Exclusion criteria
Patients eligible for this study must not have met any of the following criteria: * Patients who failed prior attempts at allogeneic HSCT * Patients who had received an autologous transplant * Patients with Acute GVHD Grade III-IV * Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis. * Impaired cardiac function including any of the following: * Screening ECG with a QTc \> 450 msec. If QTc \> 450 and electrolytes were not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc. * Patients with congenital long QT syndrome * History or presence of sustained ventricular tachycardia * Any history of ventricular fibrillation or torsades de pointes * Bradycardia defined as HR. \< 50 bpm * Right bundle branch block + left anterior hemiblock (bifascicular block) * Patients with myocardial infarction or unstable angina \< 6 months prior to starting study * Congestive Heart Failure NY Heart Association class III or IV * Patients with an ejection fraction \< 45% assessed by MUGA or ---ECHO within 28 days prior to starting study cycle 1 (of midostaurin or control group) * Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolves to ≤ Grade 1 within screening timeframe) * Patient required treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers other than those required for GVH or infection prophylaxis or treatment Pregnant or nursing (lactating) women, or women of child-bearing potential, must have used highly effective methods of contraception during dosing and for 30 days after treatment completion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | date of transplant up to 18 months | Relapse-free survival assesses the clinical benefit of remaining in remission free from relapse or death due to the disease. It was defined as the time from transplant to relapse or death due to the disease. Relapse following complete response was defined as reappearance of leukemic blasts in the peripheral blood or finding more than 5% blasts in the bone marrow. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | date of transplant up to 24 months | DFS was defined as the time from transplant to relapse or death due to any cause. If a patient had more than 1 event (e.g., relapse then death) then the earliest date was taken into account. |
| Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | date of transplant up to 24 months | Relapse-free survival was defined as the time from transplant to relapse or death due to the disease 24 months post-transplant. If a patient had more than one event (e.g., relapse then death) then the earliest date was taken into account. |
| Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | date of transplant up to 24 months | Overall survival was defined as the time from transplant to death due to any cause. |
| Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | Randomization to 18 months | Relapse-free survival assesses the clinical benefit of remaining in remission free from relapse or death due to the disease. It was defined as the time from transplant to relapse or death due to the disease. Relapse following complete response was defined as reappearance of leukemic blasts in the peripheral blood or finding more than 5% blasts in the bone marrow. |
| FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio. | up to 24 months from date of transplannt or at study completion | Unable to retrieve a sufficient amount of archived samples to perform an analysis therefore the study was not able to verify the FLT3-ITD mutation status |
| Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Pre-dose on days 1 and 15 of Cycle 1, on day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data. Values below the lower limit of quantification (LLOQ) will be treated as zero in any calculations of summary statistics. |
| Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | date of transplant up to 24 months | Non-relapse mortality (NRM) was defined as the time from transplant to death due to reasons other than relapse/progressive disease |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care With Midostaurin Patients received standard of care in the post stem cell transplant (SCT) setting in addition to Midostaurin 50mg twice a day for 12 months (cycles). | 30 |
| Standard of Care Patients received standard of care alone in the post SCT setting | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Treatment Follow-up | Administrative problems | 2 | 0 |
| Post Treatment Follow-up | Death | 8 | 4 |
| Post Treatment Follow-up | Lost to Follow-up | 1 | 4 |
| Post Treatment Follow-up | Protocol Violation | 0 | 1 |
| Post Treatment Follow-up | Relapse | 1 | 2 |
| Post Treatment Follow-up | Withdrawal by Subject | 4 | 3 |
| Treatment | Administrative problems | 4 | 1 |
| Treatment | Adverse Event | 1 | 8 |
| Treatment | Randomized, not treated | 1 | 1 |
| Treatment | Relapse | 4 | 2 |
| Treatment | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | Standard of Care With Midostaurin | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 13.68 | 46.0 years STANDARD_DEVIATION 11.08 | 48.4 years STANDARD_DEVIATION 12.58 |
| Body Mass Index | 26.9934 kg/m^2 STANDARD_DEVIATION 7.11368 | 26.6400 kg/m^2 STANDARD_DEVIATION 5.27475 | 26.8101 kg/m^2 STANDARD_DEVIATION 6.17055 |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 27 participants | 27 participants | 54 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 14 Participants | 12 Participants | 26 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 0 / 30 | 1 / 60 |
| other Total, other adverse events | 28 / 30 | 26 / 30 | 54 / 60 |
| serious Total, serious adverse events | 9 / 30 | 15 / 30 | 24 / 60 |
Outcome results
Primary
Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis
Relapse-free survival assesses the clinical benefit of remaining in remission free from relapse or death due to the disease. It was defined as the time from transplant to relapse or death due to the disease. Relapse following complete response was defined as reappearance of leukemic blasts in the peripheral blood or finding more than 5% blasts in the bone marrow.
Time frame: date of transplant up to 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.80 proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.76 proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.93 proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.89 proportion of participants |
p-value: 0.265595% CI: [0.12, 1.86]Log Rank
Secondary
FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio.
Unable to retrieve a sufficient amount of archived samples to perform an analysis therefore the study was not able to verify the FLT3-ITD mutation status
Time frame: up to 24 months from date of transplannt or at study completion
Population: Insufficient amount of samples to perform analysis
Secondary
Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels
Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data. Values below the lower limit of quantification (LLOQ) will be treated as zero in any calculations of summary statistics.
Time frame: Pre-dose on days 1 and 15 of Cycle 1, on day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: number of samples available differed across time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 14,Cycle 11 Day 1 | 718.22 ng/ml | Standard Deviation 538.208 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 11,Cycle 8 Day 1 | 537.95 ng/ml | Standard Deviation 229.529 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 8,Cycle5,Day 1 | 525.73 ng/ml | Standard Deviation 255.032 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 5,Cycle2,Day 1 | 769.92 ng/ml | Standard Deviation 485.353 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 10,Cycle 7 Day 1 | 754.95 ng/ml | Standard Deviation 497.976 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 9,Cycle6,Day 1 | 519.10 ng/ml | Standard Deviation 328.032 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 2,Cycle1,Day 1 | 17.46 ng/ml | Standard Deviation 76.806 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 4,Cycle1, Day 15 | 932.46 ng/ml | Standard Deviation 770.597 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 13,Cycle 10 Day 1 | 643.07 ng/ml | Standard Deviation 452.268 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 6,Cycle3,Day 1 | 907.20 ng/ml | Standard Deviation 528.017 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 15,Cycle 12 Day 1 | 564.69 ng/ml | Standard Deviation 410.156 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 12,Cycle 9 Day 1 | 571.76 ng/ml | Standard Deviation 311.764 |
| Standard of Care With Midostaurin | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 7,Cycle4,Day 1 | 548.45 ng/ml | Standard Deviation 459.294 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 9,Cycle6,Day 1 | 1757.86 ng/ml | Standard Deviation 685.74 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 2,Cycle1,Day 1 | 0.00 ng/ml | Standard Deviation 0 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 4,Cycle1, Day 15 | 1572.69 ng/ml | Standard Deviation 684.955 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 5,Cycle2,Day 1 | 1768.77 ng/ml | Standard Deviation 849.58 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 6,Cycle3,Day 1 | 2051.55 ng/ml | Standard Deviation 765.758 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 7,Cycle4,Day 1 | 1707.15 ng/ml | Standard Deviation 810.143 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 8,Cycle5,Day 1 | 1742.85 ng/ml | Standard Deviation 658.905 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 10,Cycle 7 Day 1 | 1717.35 ng/ml | Standard Deviation 720.259 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 11,Cycle 8 Day 1 | 1787.21 ng/ml | Standard Deviation 733.162 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 12,Cycle 9 Day 1 | 1889.76 ng/ml | Standard Deviation 678.435 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 13,Cycle 10 Day 1 | 1836.50 ng/ml | Standard Deviation 632.894 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 14,Cycle 11 Day 1 | 1857.33 ng/ml | Standard Deviation 868.406 |
| Standard of Care | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 15,Cycle 12 Day 1 | 1706.29 ng/ml | Standard Deviation 643.326 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 11,Cycle 8 Day 1 | 774.84 ng/ml | Standard Deviation 326.583 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 6,Cycle3,Day 1 | 929.45 ng/ml | Standard Deviation 311.841 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 14,Cycle 11 Day 1 | 983.94 ng/ml | Standard Deviation 801.361 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 12,Cycle 9 Day 1 | 850.47 ng/ml | Standard Deviation 328.411 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 5,Cycle2,Day 1 | 779.90 ng/ml | Standard Deviation 400.244 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 2,Cycle1,Day 1 | 16.89 ng/ml | Standard Deviation 61.212 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 13,Cycle 10 Day 1 | 851.38 ng/ml | Standard Deviation 347.311 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 9,Cycle6,Day 1 | 763.86 ng/ml | Standard Deviation 408.29 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 8,Cycle5,Day 1 | 722.00 ng/ml | Standard Deviation 320.977 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 4,Cycle1, Day 15 | 906.57 ng/ml | Standard Deviation 747.836 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 10,Cycle 7 Day 1 | 780.65 ng/ml | Standard Deviation 424.2 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 7,Cycle4,Day 1 | 714.00 ng/ml | Standard Deviation 610.925 |
| Metabolite CGP62221 | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Visit 15,Cycle 12 Day 1 | 763.60 ng/ml | Standard Deviation 387.685 |
Secondary
Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis
Non-relapse mortality (NRM) was defined as the time from transplant to death due to reasons other than relapse/progressive disease
Time frame: date of transplant up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.96 proportion of participants |
| Standard of Care With Midostaurin | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.96 proportion of participants |
| Standard of Care With Midostaurin | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.92 proportion of participants |
| Standard of Care With Midostaurin | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.92 proportion of participants |
| Standard of Care | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.96 proportion of participants |
| Standard of Care | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 1.00 proportion of participants |
| Standard of Care | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.96 proportion of participants |
| Standard of Care | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.96 proportion of participants |
p-value: 0.416995% CI: [0.09, 2.74]Log Rank
Secondary
Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis
Overall survival was defined as the time from transplant to death due to any cause.
Time frame: date of transplant up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.96 proportion of participants |
| Standard of Care With Midostaurin | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.89 proportion of participants |
| Standard of Care With Midostaurin | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.76 proportion of participants |
| Standard of Care With Midostaurin | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.76 proportion of participants |
| Standard of Care | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.85 proportion of participants |
| Standard of Care | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 1.00 proportion of participants |
| Standard of Care | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.85 proportion of participants |
| Standard of Care | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.89 proportion of participants |
p-value: 0.341895% CI: [0.19, 1.79]Log Rank
Secondary
Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis
Relapse-free survival assesses the clinical benefit of remaining in remission free from relapse or death due to the disease. It was defined as the time from transplant to relapse or death due to the disease. Relapse following complete response was defined as reappearance of leukemic blasts in the peripheral blood or finding more than 5% blasts in the bone marrow.
Time frame: Randomization to 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.80 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.76 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.93 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.85 Proportion of participants |
p-value: 0.429795% CI: [0.17, 2.14]Log Rank
Secondary
Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis
DFS was defined as the time from transplant to relapse or death due to any cause. If a patient had more than 1 event (e.g., relapse then death) then the earliest date was taken into account.
Time frame: date of transplant up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.90 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.77 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.69 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.69 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.81 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.85 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.89 Proportion of participants |
p-value: 0.242495% CI: [0.2, 1.52]Log Rank
Secondary
Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis
Relapse-free survival was defined as the time from transplant to relapse or death due to the disease 24 months post-transplant. If a patient had more than one event (e.g., relapse then death) then the earliest date was taken into account.
Time frame: date of transplant up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.80 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.76 Proportion of participants |
| Standard of Care With Midostaurin | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.76 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 24 months | 0.85 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 6 months | 0.93 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 18 months | 0.89 Proportion of participants |
| Standard of Care | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | 12 months | 0.93 Proportion of participants |
p-value: 0.429795% CI: [0.17, 2.14]Log Rank
Post Hoc
All Collected Deaths
On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 12.5 months (treatment duration ranged from 0.2 to 11.5 months). Deaths post treatment survival follow up were collected after the on treatment period, up to approximately 51 months.
Time frame: approx. 12.5 months, approx. 51 months
Population: Clinical Database Population: all treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care With Midostaurin | All Collected Deaths | Total Deaths | 8 Participants |
| Standard of Care With Midostaurin | All Collected Deaths | Deaths on-treatment | 1 Participants |
| Standard of Care | All Collected Deaths | Total Deaths | 4 Participants |
| Standard of Care | All Collected Deaths | Deaths on-treatment | 0 Participants |