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

NCT03280030

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study in Asia and Russia of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML
  • Official Title: A Phase II, Randomized, Double-blind, Multi-center, Placebo-controlled Study in Asia and Russia to Evaluate the Efficacy and Safety of Twice Daily Oral 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).

Clinical Trial IDs

  • ORG STUDY ID: CPKC412A2220
  • NCT ID: NCT03280030

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
MidostaurinPKC412Midostaurin
PlaceboPlacebo

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
MidostaurinExperimentalPatients will take study drug on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
  • Midostaurin
PlaceboPlacebo ComparatorPatients will take placebo on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
  • Placebo

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:

               -  Serum creatinine < 1.5 mg/dL

               -  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

        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

          -  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.
      
Maximum Eligible Age:64 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Safety Evetnts (Part 1, Japan only)
Time Frame:Day 21 of the first Consolidation cycle
Safety Issue:
Description:Incidence and severity of Safety Events, defined as death or serious adverse event leading to treatment discontinuation that occurs on or before Day 21 of the first Consolidation cycle. This is is determined by the Independent Safety Committee to be definitely or probably related to midostaurin.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:51 months
Safety Issue:
Description:Overall survival defined as the time from the date of randomization to date of death due to any cause
Measure:Complete Remission
Time Frame:51 months
Safety Issue:
Description:Complete Remission defined as the proportion of patients with a CR according to Chelson Criteria, at various timepoints
Measure:Cumulative incidence of relapse (CIR)
Time Frame:51 months
Safety Issue:
Description:CIR (only for patients who have achieved CR after study treatment initiation), is measured from the date of first CR to relapse or death due to AML, whichever occurs first.
Measure:Metabolite CGP52421
Time Frame:Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12
Safety Issue:
Description:Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421
Measure:Metabolite CGP62221
Time Frame:Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12
Safety Issue:
Description:Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221.
Measure:Quality of life (QoL) per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30
Time Frame:Screening, D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year
Safety Issue:
Description:EORTC)QLQ-C30 total score and functional scales scores as determined by the score and absolute change from baseline at each scheduled assessment.
Measure:Quality of life (QoL) per Patient Global Impression of Change (PGIC)
Time Frame:D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year
Safety Issue:
Description:PGIC score determined frequencies and percentages by scheduled timepoint.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • midostaurin
  • PKC412
  • cytarabine
  • daunorubicin
  • acute myeloid leukemia
  • combination treatment
  • FLT3
  • acute myeloid leukemia (AML)
  • acute myelogenous leukemia (AML)

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