Phase 3
Completed N=501
A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)
Source: ClinicalTrials.gov NCT03512197 ↗Enrolled (actual)
501
Serious AEs
42.3%
Results posted
Jun 2023
Primary outcomePrimary: Event Free Survival (EFS) — 5.98; 5.88 Months
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Event Free Survival (EFS) |
5.98; 5.88 | — |
| SECONDARY Overall Survival (OS) (Key Secondary) |
NA; 19.22 | — |
| SECONDARY Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematological Recovery (CRi) But With Adequate Blood Count Recovery Rate. |
59.2; 61.0 | — |
| SECONDARY Percentage of Participants With Minimal Residual Disease (MRD) Negative Status |
40.8; 41.0 | — |
| SECONDARY Percentage of Participants With Minimal Residual Disease (MRD) Negative Status During Post-consolidation Phase |
33.3; 33.3 | — |
| SECONDARY Time to Measurable Residual Disease (MRD) Negativity by Flow Cytometry |
2.27; 2.07 | — |
| SECONDARY Disease-free Survival (DFS) |
10.5; 9.1 | — |
| SECONDARY Cumulative Incidence of Relapse (CIR) |
5.1; 6.6 | — |
| SECONDARY Cumulative Incidence of Death (CID) |
NA; NA | — |
| SECONDARY Time to CR or CRi With Adequate Blood Count Recovery |
1.12; 1.15 | — |
| SECONDARY Time to Partial and Full Neutrophil Recovery |
1.1; 0.9; 1.2; 1.1 | — |
| SECONDARY Time to Partial and Full Platelet Recovery |
NA; NA; 0.953; 0.887 | — |
| SECONDARY Plasma Concentrations for Midostaurin and Its Metabolites: CGP52421 and CGP62221 for Non-poor Metabolizers |
0; 0; 0; 1110; 30.0; 37.6 | — |
| SECONDARY AUC0-t: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 |
14800; 712; 1830 | — |
| SECONDARY AUClast: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 |
12200; 493; 1130 | — |
| SECONDARY Cmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 |
1910; 74.7; 183 | — |
| SECONDARY Tmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8 |
3.28; 5.38; 7.17 | — |
| SECONDARY Total Score for Each Time Point for the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) |
122.8; 123.1; 123.9; 122.1; 124.8; 123.5 | — |
| SECONDARY Scores for Each Time Point for the EQ5D-5L (a Visual Analogue Scale (VAS)) |
62.7; 64.3; 67.9; 64.4; 68.1; 64.0 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of AML (≥20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL with PML-RARA are not eligible.
- Suitability for intensive induction chemotherapy in the judgment of the investigator
- Documented absence of an ITD and TKD activating mutation at codons D835 and I836 in the FLT3 gene, as determined by analysis in a Novartis designated laboratory using a validated clinical trial assay with clinical cutoff of 0.05 mutant to wild type signal ratio
- Age ≥18 years
- Laboratory values that indicate adequate organ function assessed locally at the screening visit
Exclusion Criteria
- Central nervous system (CNS) leukemia
- Therapy-related secondary AML
- Isolated extramedullary leukemia
- Prior therapy for leukemia or myelodysplasia
- AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment (e.g., azacytidine or decitabine)
- Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)
Data sourced from ClinicalTrials.gov (NCT03512197). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.