Study of Crenolanib vs Midostaurin Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed FLT3 Mutated AML
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Crenolanib Crenolanib following salvage chemotherapy |
Drug: Crenolanib
Crenolanib will be administered orally
Other Names:
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
- Event-free survival (EFS) [5 years]
Secondary Outcome Measures
- Overall Survival [7 years]
- Relapse free survival [5 years]
- Composite complete remission rate [5 years]
- Duration of response [5 years]
Eligibility Criteria
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)
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.- ARO-021