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)

ClinicalTrials.gov Identifier: NCT03512197

Novartis Reference Number: CPKC412E2301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is 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 will evaluate 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.

Condition 
Acute Myeloid Leukemia (AML)
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
513 participants
Start date 
Aug 25, 2010
Completion date 
Jan 25, 2021
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Midostaurin
After randomization, patients will receive midostaurin twice daily until not achieving CR nor CRi, relapse after CR or CRi, intolerable toxicity, or consent withdrawal
Drug
Midostaurin Placebo
After randomization, patients will receive midostaurin placebo twice daily until not achieving CR nor CRi, relapse after CR or CRi, intolerable toxicity, or consent withdrawal
Drug
Chemotherapy
Along with the study drug/placebo, chemotherapy will be give as welll: either Daunorubicin or Idarubicin and Cytarabine al take by i.v.

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)

Study Locations

United States
University of Chicago Medical Center
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Chicago, 60637
Illinois
United States
Dana Farber Cancer Institute
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Boston, 02115
Massachusetts
United States
Oregon Health and Science University
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Portland, 97239
Oregon
United States
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Caba, C1118AAT
Buenos Aires
Argentina
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Westmead, 2145
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Woolloongabba, 4102
Queensland
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Prahran, 3181
Victoria
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Murdoch, 6150
Western Australia
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Linz, A-4010
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Austria
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Vienna, 1140
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Austria
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Wien, 1090
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Austria
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Antwerpen, 2060
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Brugge, 8000
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Roeselare, 8800
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Porto Alegre, 90035-003
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