Study of Crenolanib vs Midostaurin Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed FLT3 Mutated AML

Sponsor
Arog Pharmaceuticals, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03258931
Collaborator
(none)
510
31
2
74.6
16.5
0.2

Study Details

Study Description

Brief Summary

A phase III randomized multi-center study designed to compare the efficacy of crenolanib with that of midostaurin when administered following induction chemotherapy, consolidation chemotherapy and bone marrow transplantation in newly diagnosed AML subjects with FLT3 mutation. About 510 subjects will be randomized in a 1:1 ratio to receive either crenolanib in addition to standard first line treatment of AML (chemotherapy and if eligible, transplantation) (arm A) or midostaurin and standard treatment (arm B). Potentially eligible subjects will be registered and tested for the presence of FLT3 mutation. Once the FLT3 mutation status is confirmed and additional eligibility is established, subject will be randomized and enter into the treatment phase.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
510 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Randomized Study of Crenolanib Versus Midostaurin Administered Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed Subjects With FLT3 Mutated Acute Myeloid Leukemia
Actual Study Start Date :
Aug 15, 2018
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Nov 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Crenolanib

Crenolanib following salvage chemotherapy

Drug: Crenolanib
Crenolanib will be administered orally
Other Names:
  • Crenolanib besylate
  • Drug: Cytarabine
    100 mg/m² IV continuous infusion over 24 hours

    Drug: Duanorubicin
    90 mg/m2 IV

    Active Comparator: Midostaurin

    Midostaurin following salvage chemotherapy

    Drug: Midostaurin
    Midostaurin will be administered orally

    Drug: Cytarabine
    100 mg/m² IV continuous infusion over 24 hours

    Drug: Duanorubicin
    90 mg/m2 IV

    Outcome Measures

    Primary Outcome Measures

    1. Event-free survival (EFS) [5 years]

    Secondary Outcome Measures

    1. Overall Survival [7 years]

    2. Relapse free survival [5 years]

    3. Composite complete remission rate [5 years]

    4. Duration of response [5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Confirmed diagnosis of de novo AML according to World Health Organization (WHO) 2016 classification

    • Presence of FLT3-ITD and/or D835 mutation(s) in bone marrow or peripheral blood

    • Age ≥ 18 years and ≤ 60 years

    • Adequate hepatic function within 48 hours prior to induction chemotherapy

    • Adequate renal functions within 48 hours prior to induction chemotherapy

    • ECOG performance status within 48 hours prior to induction chemotherapy ≤ 3

    • Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy specified

    Exclusion Criteria:
    • Acute promyelocytic leukemia (APL)

    • Known clinically active central nervous system (CNS) leukemia

    • Severe liver disease

    • Active infections

    • Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)

    • Known infection with human immunodeficiency virus (HIV)

    • Prior systemic anti-cancer treatment (e.g. chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents)(except for hydroxyurea and/or leukapheresis)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010
    2 Ronald Reagan UCLA Medical Center Los Angeles California United States 90095
    3 US Davis Health Sacramento California United States 95817
    4 Yale Cancer Center New Haven Connecticut United States 06510
    5 Moffitt Cancer Center Tampa Florida United States 33612
    6 Rush Medical Center Chicago Illinois United States 60612
    7 University of Illinois at Chicago Chicago Illinois United States 60612
    8 University of Chicago Chicago Illinois United States 60637
    9 Indiana University Indianapolis Indiana United States 46206-5149
    10 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    11 University of Kansas Kansas City Kansas United States 66160
    12 Massachusetts General Hospital Boston Massachusetts United States 02114
    13 Beth Israel Deacnss Medical Center Oncology Boston Massachusetts United States 02215
    14 Dana-Farber Cancer Insitute Boston Massachusetts United States 02215
    15 Karmanos Cancer Institute Detroit Michigan United States 48201
    16 Henry Ford Health System Detroit Michigan United States 48202
    17 University of Minnesota Minneapolis Minnesota United States 55455
    18 John Theurer Cancer Center at Hackensack UMC Hackensack New Jersey United States 07601
    19 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
    20 Montefiore Medical Center Bronx New York United States 10467
    21 Roswell PArk Buffalo New York United States 14263
    22 New York University New York New York United States 10016
    23 Mount Sinai New York New York United States 10029-6574
    24 Columbia University New York New York United States 10032
    25 Cornell University New York New York United States 10065
    26 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
    27 University of Rochester Medical Center New York New York United States 14642
    28 The UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27514
    29 Wake Forest Baptist Health, Section on Hematology & Oncology Winston-Salem North Carolina United States 27157
    30 Oregon Health and Science University Portland Oregon United States 97239
    31 University of Virginia Health System Charlottesville Virginia United States 22908

    Sponsors and Collaborators

    • Arog Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Arog Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03258931
    Other Study ID Numbers:
    • ARO-021
    First Posted:
    Aug 23, 2017
    Last Update Posted:
    May 22, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 22, 2020