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

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

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 Overview

• Status: Recruiting
• Conditions: Newly Diagnosed FLT3 Mutated AML
• Intervention / Treatment: Drug: Crenolanib; Drug: Cytarabine; Drug: Duanorubicin; Drug: Midostaurin

• Study Type: Interventional
• Enrollment (Anticipated): 510
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: General Contact; Phone Number: 214-593-0500; Email: info@arogpharma.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
      • Contact: Chatchada Karanes, MD; Phone Number: 626-218-2405; Email: CKaranes@coh.org
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Ronald Reagan UCLA Medical Center
      • Contact: Caspian Oliai, MD; Phone Number: 310-206-5756; Email: COliai@mednet.ucla.edu
    • Sacramento, California, United States, 95817
      • Recruiting
      • US Davis Health
      • Contact: Brian Jonas, MD; Phone Number: 800-282-3284; Email: bajonas@ucdavis.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
      • Contact: Nikolai Podoltsev, MD; Phone Number: 203-737-7059; Email: nikolai.podoltsev@yale.edu
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Kendra Sweet, MD; Phone Number: 813-745-6841; Email: Kendra.Sweet@moffitt.org
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Contact: Hongtao Liu, MD; Phone Number: 773-834-0589; Email: hliu2@medicine.bsd.uchicago.edu
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois at Chicago
      • Contact: John G Quigley, MD; Phone Number: 312-413-1300; Email: seanq@uic.edu
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Rush Medical Center
      • Contact: Melissa Larson, MD; Phone Number: 312-942-5978; Email: melissa_larson@rush.edu
  • Indiana
    • Indianapolis, Indiana, United States, 46206-5149
      • Recruiting
      • Indiana University
      • Contact: Heiko Konig, MD; Phone Number: 317-274-3590; Email: hkonig@iupui.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
      • Contact: Carlos Vigil-Gonzales, MD; Phone Number: 319-356-1206; Email: carlos-vigil@uiowa.edu
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas
      • Contact: Sunil Abhyankar, MD; Phone Number: 913-588-9281; Email: sabhyankar@kumc.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Amir Fathi, MD; Phone Number: 617-724-1124; Email: AFATHI@mgh.harvard.edu
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deacnss Medical Center Oncology
      • Contact: Malgorzata McMasters, MD; Phone Number: 617-667-9920; Email: mmcmaste@bidmc.harvard.edu
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Insitute
      • Contact: Richard M Stone, MD; Phone Number: 617-632-2214; Email: Richard_Stone@dfci.harvard.edu
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Contact: Yue Guo, MD; Phone Number: 800-436-7936; Email: YGUO1@hfhs.org
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
      • Contact: Jay Yang, MD; Phone Number: 800-527-6266; Email: yangj@karmanos.org
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Erica Warlick, MD; Phone Number: 612-625-5467; Email: ewarlick@umn.edu
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center At Hackensack UMC
      • Contact: Jamie Koprivnikar, MD; Phone Number: 551-996-5900; Email: Jamie.Koprivnikar@hackensackmeridian.org
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
      • Contact: Athena Kritharis, MD; Phone Number: 732-235-4439; Email: athena.kritharis@rutgers.edu
  • New York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: Aditi Shastri, MD; Phone Number: 718-920-4826; Email: ASHASTRI@montefiore.org
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park
      • Contact: Eunice S Wang, MD; Phone Number: 716-845-3544; Email: eunice.wang@roswellpark.org
    • New York, New York, United States, 10016
      • Recruiting
      • New York University
      • Contact: Mohammad Abdul Hay, MD; Phone Number: 646-501-4818; Email: maher.abdulhay@nyulangone.org
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Joseph Jurcic, MD; Phone Number: 646-317-5077; Email: jgj2110@cumc.columbia.edu
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center
      • Contact: Aaron Goldberg, MD; Phone Number: 212-639-2126; Email: goldbera@mskcc.org
    • New York, New York, United States, 10029-6574
      • Recruiting
      • Mount Sinai
      • Contact: John Mascarenhas, MD; Phone Number: 212-241-3417; Email: John.mascarenhas@mssm.edu
    • New York, New York, United States, 10065
      • Recruiting
      • Cornell University
      • Contact: Pinkal Desai, MD; Phone Number: 646-962-2700; Email: pid9006@med.cornell.edu
    • New York, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Jane Liesveld, MD; Phone Number: 585-275-5295; Email: jane_liesveld@urmc.rochester.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • The UNC Lineberger Comprehensive Cancer Center
      • Contact: Joshua Zeidner, MD; Phone Number: 919-966-4432; Email: joshua_zeidner@med.unc.edu
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Health, Section on Hematology & Oncology
      • Contact: Rupali Roy Bhave, MD; Phone Number: 336-713-0864; Email: rbhave@wakehealth.edu
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Contact: Elie Traer, MD; Phone Number: 503-418-9614; Email: traere@ohsu.edu
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Health System
      • Contact: Michael Keng, MD; Phone Number: 319-356-1206; Email: MK2PV@hscmail.mcc.virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Cytarabine; 100 mg/m² IV continuous infusion over 24 hours; Drug: Duanorubicin; 90 mg/m2 IV; Drug: Midostaurin; Midostaurin will be administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival (EFS)	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response	5 years
Relapse free survival	5 years
Overall Survival	7 years
Composite complete remission rate	5 years

Collaborators and Investigators

• Sponsor: Arog Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 21, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Cytarabine; Midostaurin; Crenolanib
• Other Study ID Numbers: ARO-021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No