Phase 3
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)
Acute Myeloid Leukemia (AML)
Bottom Line
View on ClinicalTrials.gov: NCT03512197 ↗Enrolled (actual)
501
Serious AEs
42.3%
Results posted
Jun 2023
Primary outcome: Primary: Event Free Survival (EFS) — 5.98; 5.88 Months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Midostaurin (Drug); Placebo (Drug); Chemotherapy (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Feb 2021
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 | — |
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.
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.