Clinical trial · Interventional
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)
A Phase III, Randomized, Double-blind Study of Chemotherapy With Daunorubicin or Idarubicin and Cytarabine for Induction and Intermediate Dose Cytarabine for Consolidation Plus Midostaurin (PKC412) or Chemotherapy Plus Placebo in Newly Diagnosed Patients With FLT-3 Mutation Negative Acute Myeloid Leukemia (AML)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia (AML) | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Chemotherapy | Drug | Chemotherapy | ALIAS |
| Midostaurin | Drug | Midostaurin | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Midostaurin + chemotherapy
- description
- Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.
- interventionNames
- Drug: Midostaurin
- Drug: Chemotherapy
- type
- PLACEBO_COMPARATOR
- label
- Placebo + chemotherapy
- description
- Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 1. Diagnosis of AML (≥20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL with PML-RARA are not eligible. 2. Suitability for intensive induction chemotherapy in the judgment of the investigator 3. 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 4. Age ≥18 years 5. Laboratory values that indicate adequate organ function assessed locally at the screening visit Exclusion Criteria: 1. Central nervous system (CNS) leukemia 2. Therapy-related secondary AML 3. Isolated extramedullary leukemia 4. Prior therapy for leukemia or myelodysplasia 5. AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment (e.g., azacytidine or decitabine) 6. Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)
References
Publications (1)
- DERIVEDSechaud R, Peters T, Gu H, Rahmanzadeh G, Sharma GK, Guichard N, Menssen HD. Pharmacogenomic, pharmacokinetic, and safety analysis of CYP3A4/CYP3A5 polymorphisms of midostaurin in patients with acute myeloid leukemia. Eur J Clin Pharmacol. 2025 Dec 23;82(1):19. doi: 10.1007/s00228-025-03971-y. PMID 41432755