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

NCT03258931 | Completed Phase 3 FDA Drug

• 1 other identifier: ARO-021
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 31

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.

Conditions

Newly Diagnosed FLT3 Mutated AML

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  5 years

Secondary Outcomes (4)

• Overall Survival

  7 years

• Relapse free survival

  5 years

• Composite complete remission rate

  5 years

• Duration of response

  5 years

Study Arms (2)

Crenolanib

EXPERIMENTAL

Crenolanib following salvage chemotherapy

Drug: Crenolanib; Drug: Cytarabine; Drug: Duanorubicin

Midostaurin

ACTIVE COMPARATOR

Midostaurin following salvage chemotherapy

Drug: Midostaurin; Drug: Cytarabine; Drug: Duanorubicin

Interventions

Crenolanib DRUG

Crenolanib will be administered orally

Also known as: Crenolanib besylate

Crenolanib

Midostaurin DRUG

Midostaurin will be administered orally

Midostaurin

Cytarabine DRUG

100 mg/m² IV continuous infusion over 24 hours

Crenolanib; Midostaurin

Duanorubicin DRUG

90 mg/m2 IV

Crenolanib; Midostaurin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead

Study Sites (31)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

US Davis Health

Sacramento, California, 95817, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Rush Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46206-5149, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deacnss Medical Center Oncology

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Insitute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Roswell Park

Buffalo, New York, 14263, United States

Location

New York University

New York, New York, 10016, United States

Location

Mount Sinai

New York, New York, 10029-6574, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cornell University

New York, New York, 10065, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester Medical Center

New York, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

The UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514, United States

Location

Wake Forest Baptist Health, Section on Hematology & Oncology

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Interventions

crenolanib; midostaurin; Cytarabine

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 23, 2017
• Study Start: August 15, 2018
• Primary Completion: April 6, 2026
• Study Completion: April 6, 2026
• Last Updated: April 9, 2026

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (31)