Clinical trial NCT03258931: Study of Crenolanib vs Midostaurin Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed FLT3 Mutated AML
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Newly Diagnosed FLT3 Mutated AML
Lead sponsor: Arog Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-23
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 7 years
measure: Relapse free survival
timeFrame: 5 years
measure: Composite complete remission rate
timeFrame: 5 years
measure: Duration of response
timeFrame: 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: US Davis Health
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Rush Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deacnss Medical Center Oncology
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Insitute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack UMC
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell PArk
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: The UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health, Section on Hematology & Oncology
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
References: