Phase 2
N=5
A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML
Acute Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT03280030 ↗Enrolled (actual)
5
Serious AEs
36.4%
Results posted
Feb 2025
Primary outcome: Primary: Percentage of Safety Events (Part 1, Japan Only) — 5; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Midostaurin (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Nov 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Safety Events (Part 1, Japan Only) |
5; 0 | — |
| PRIMARY Event Free Survival (EFS) (Part 2 - Randomized, Controlled) |
7.6; NA | — |
| SECONDARY Overall Survival |
NA; NA | — |
| SECONDARY Percentage of Participants With Complete Remission (CR) |
70.0; 78.1; 6.7; 0.0; 56.7; 65.6 | — |
| SECONDARY Percentage of Participants With Cumulative Incidence of Relapse (CIR) |
21; 25 | — |
| SECONDARY Pharmakinetics (PK) for Midostaurin: AUClast & AUC0-t |
17900; 19200 | — |
| SECONDARY Pharmakinetics (PK) for Midostaurin: Cmax |
2420 | — |
| SECONDARY Metabolite CGP52421: PK Parameters AUClast, AUC0-t |
754; 876 | — |
| SECONDARY Metabolite CGP52421: PK Parameter Cmax |
98.6 | — |
| SECONDARY Metabolite CGP62221: PK Parameters: AUClast, AUC0-t |
1430; 1730 | — |
| SECONDARY Metabolite CGP62221: PK Parameter: Cmax |
196 | — |
| SECONDARY Change From Baseline in Quality of Life (QoL) Per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 |
27.8; 0.0; 20.8; 37.1; 28.3; 27.8 | — |
| SECONDARY Quality of Life (QoL) Per Patient Global Impression of Change (PGIC) |
1; 0; 2; 1; 3; 0 | — |
Summary
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).
Eligibility Criteria
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:
- Estimated creatinine clearance ≥ 30 ml/min
- Total bilirubin ≤ 1.5 x ULN, except in the setting of isolated Gilbert syndrome
- Aspartate transaminase (AST) ≤ 3.0 x ULN
- Alanine transaminase (ALT) ≤ 3.0 x ULN
- Suitability for intensive chemotherapy in the judgment of the investigator
Exclusion Criteria
- Neurologic symptoms suggestive of CNS leukemia unless CNS leukemia has been excluded by a lumbar puncture. Patients with CSF fluid positive for AML blasts are not eligible
- Developed therapy-related AML after prior radiotherapy (RT) or chemotherapy for another cancer or disorder
- Known hypersensitivity to midostaurin, cytarabine or daunorubicin or to any of the excipients of midostaurin/placebo, cytarabine or daunorubicin
- Abnormal chest X-ray unless the abnormality represents a non-active, or non-clinically significant finding, such as scarring (subjects with controlled non active lung infection are eligible)
- Known impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin
- Cardiac or cardiac repolarization abnormality
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 4 months after stopping medication
Data sourced from ClinicalTrials.gov (NCT03280030). 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.