A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML

• Status: Active, not recruiting
• Trial end date: 2022-11-21
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate 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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: 4'-N-benzoylstaurosporine; Cytarabine; Daunorubicin; Midostaurin; Staurosporine

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 Other protocol-defined Inclusion/Exclusion criteria may apply.