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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Newly Diagnosed FLT3 Mutated AML

Intervention / Treatment
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* Drug: Crenolanib
* Drug: Midostaurin
* Drug: Cytarabine
* Drug: Duanorubicin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crenolanib<br>Crenolanib following salvage chemotherapy | Drug: Crenolanib<br>* Crenolanib will be administered orally<br>* Other names: Crenolanib besylate;Drug: Cytarabine<br>* 100 mg/m² IV continuous infusion over 24 hours<br>Drug: Duanorubicin<br>* 90 mg/m2 IV<br>|
| Active Comparator: Midostaurin<br>Midostaurin following salvage chemotherapy | Drug: Midostaurin<br>* Midostaurin will be administered orally<br>Drug: Cytarabine<br>* 100 mg/m² IV continuous infusion over 24 hours<br>Drug: Duanorubicin<br>* 90 mg/m2 IV<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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