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)

JRCT ID: jRCT2080224610

Registered date:26/03/2019

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: acute myeloid leukemia
• Date of first enrollment: 22/10/2018
• Target sample size: 502
• Countries of recruitment: Japan,Asia except Japan,North America,South America,Europe
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : midostaurin
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : 50 mg, bid, oral

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

Outcome(s)

• Primary Outcome: To determine if the addition of midostaurin to standard induction and consolidation therapy, followed by single agent post-consolidation therapy improves event-free survival (EFS)

Secondary Outcome

safety
efficacy
exploratory
pharmacokinetics
To compare the rate of complete remission (CR + CRi with adequate blood count recovery) in the two treatment groups.
To compare the percentage of patients who reached MRD negative status in the two treatment groups.
To compare the percentage of patients with MRD negative status in the post-consolidation phase in the two treatment groups.
To compare the time to MRD negative status bone marrow between the two treatment groups.
To compare disease-free survival (DFS), as well as the cumulative incidence of relapse (CIR) and cumulative incidence of death (CID) in the two treatment groups.
To compare the time to CR or CRi with adequate blood count recovery in the two treatment groups.
To compare the time to neutrophil recovery in the two treatment groups.
To compare the time to platelet recovery in the two treatment groups.
To assess the safety and tolerability of midostaurin in combination with chemotherapy and as monotherapy during post-consolidation.
To further characterize the pharmacokinetics of midostaurin, CGP52421 and CGP62221.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Diagnosis of AML (>= 20% blasts in the bone marrow based on World Health Organization (WHO) 2016 classification). Patientwith acute promyelocytic leukemia APL with a PML-RARA rearrangement are not eligible.
Suitability for intensive induction chemotherapy in the judgment of the investigator based on patient performance status and comorbidities
Documented absence of an internal tandem duplication (ITD) and tyrosine kinase domain (TKD) activating mutation at codons D835 and I836 in the FLT3 gene, with clinical cutoff of 0.05 mutant to wild type signal ratio.
Other criteria specified in the protocol also apply.

Exclude criteria

Central nervous system (CNS) leukemia
Therapy-related secondary AML
Isolated extramedullary leukemia
Other criteria specified in the protocol also apply.

Related Information

• Primary Sponsor: Novartis Pharma. K.K.
• Secondary ID(s): NCT03512197,JapicCTI-194681