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

Arog Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Newly Diagnosed FLT3 Mutated AML

Treatments: Drug: Cytarabine; Drug: Duanorubicin; Drug: Crenolanib; Drug: Midostaurin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03258931

ARO-021

Details and patient eligibility

About

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.

Enrollment: 510 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

510 participants in 2 patient groups

Crenolanib

Experimental group

Description:

Crenolanib following salvage chemotherapy

Treatment:

Drug: Duanorubicin

Drug: Crenolanib

Drug: Cytarabine

Midostaurin

Active Comparator group

Description:

Midostaurin following salvage chemotherapy

Treatment:

Drug: Duanorubicin

Drug: Midostaurin

Drug: Cytarabine