Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03280030
Recruitment Status : Active, not recruiting
First Posted : September 12, 2017
Last Update Posted : October 28, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE September 8, 2017
First Posted Date  ICMJE September 12, 2017
Last Update Posted Date October 28, 2020
Actual Study Start Date  ICMJE April 6, 2018
Estimated Primary Completion Date November 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
  • Incidence of Safety Events (Part 1, Japan only) [ Time Frame: Day 21 of the first Consolidation cycle ]
    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.
  • Event Free Survival (Part 2 - randomized, controlled) [ Time Frame: 36 months ]
    Event Free survival defined as the time from the date of randomization until an EFS event is observed. An EFS event is defined as a failure to obtain a CR within an induction 2, relapse after CR, or death due to any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
  • Incidence of Safety Evetnts (Part 1, Japan only) [ Time Frame: Day 21 of the first Consolidation cycle ]
    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.
  • Event Free Survival (Part 2 - randomized, controlled) [ Time Frame: 36 months ]
    Event Free survival defined as the time from the date of randomization until an EFS event is observed. An EFS event is defined as a failure to obtain a CR within an induction 2, relapse after CR, or death due to any cause, whichever occurs first.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
  • Overall Survival [ Time Frame: 51 months ]
    Overall survival defined as the time from the date of randomization to date of death due to any cause
  • Complete Remission [ Time Frame: 51 months ]
    Complete Remission defined as the proportion of patients with a CR according to Chelson Criteria, at various timepoints
  • Cumulative incidence of relapse (CIR) [ Time Frame: 51 months ]
    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.
  • 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 ]
    Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421
  • 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 ]
    Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221.
  • 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 ]
    EORTC)QLQ-C30 total score and functional scales scores as determined by the score and absolute change from baseline at each scheduled assessment.
  • 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 ]
    PGIC score determined frequencies and percentages by scheduled timepoint.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML
Official Title  ICMJE A Phase II, Randomized, Double-blind, Multi-center, Placebo-controlled Study 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).
Brief 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Midostaurin
    Midostaurin 50 mg [two 25 mg capsules] will be administered twice per day by mouth on day 8-21 during induction and consolidation phase; then continuously during continuation phase
    Other Name: PKC412
  • Drug: Placebo
    Placebo two capsules will be administered twice per day by mouth on day 8-21 during induction and consolidation phase ; then continuously during continuation phase.
Study Arms  ICMJE
  • Experimental: Midostaurin
    Patients will take study drug on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
    Intervention: Drug: Midostaurin
  • Placebo Comparator: Placebo
    Patients will take placebo on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 27, 2020)
70
Original Estimated Enrollment  ICMJE
 (submitted: September 8, 2017)
66
Estimated Study Completion Date  ICMJE November 18, 2022
Estimated Primary Completion Date November 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hong Kong,   Japan,   Korea, Republic of,   Russian Federation,   Taiwan,   Vietnam
Removed Location Countries Thailand
 
Administrative Information
NCT Number  ICMJE NCT03280030
Other Study ID Numbers  ICMJE CPKC412A2220
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP