Study Investigating the Efficacy of Crenolanib With Chemotherapy vs Chemotherapy Alone in R/R FLT3 Mutated AML

Study Overview
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Brief Summary
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This is a randomized, multi-center, double-blind, placebo-controlled study designed to evaluate the efficacy of crenolanib administered following salvage chemotherapy, consolidation chemotherapy, post bone marrow transplantation and as maintenance in relapsed/refractory AML subjects with FLT3 activating mutation.

Official Title
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Phase III Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy of the Addition of Crenolanib to Salvage Chemotherapy Versus Salvage Chemotherapy Alone in Subjects ≤ 75 Years of Age With Relapsed/Refractory FLT3 Mutated Acute Myeloid Leukemia

Conditions
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Relapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations

Intervention / Treatment
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* Drug: Crenolanib
* Drug: Cytarabine
* Drug: Mitoxantrone
* Drug: Placebo Oral Tablet
* Drug: Fludarabine
* Drug: Idarubicin
* Drug: G-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification Presence of FLT3-ITD and/or D835 mutation(s) Subjects must be primary refractory or relapsed to 1st line intensive treatment for AML or refractory or relapsed after second line of treatment for AML Age ≥ 18 years and ≤ 75 years Adequate hepatic function Adequate renal functions ECOG performance status ≤ 3 Exclusion Criteria: Known clinically active central nervous system(CNS) leukemia Severe liver disease Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) Prior anti-leukemia therapy within the 14 days prior to randomization. Prior use of quizartinib or gilteritinib must be discontinued 21 days prior to randomization. Prior use of hydroxyurea or other palliative treatment for leukocytosis is allowed. Previous treatment with crenolanib or prior participation in clinical trial involving crenolanib.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


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>* HAM regimen FLAG-Ida<br>Drug: Mitoxantrone<br>* HAM regimen<br>Drug: Fludarabine<br>* FLAG-Ida regimen<br>Drug: Idarubicin<br>* FLAG-Ida regimen<br>Drug: G-CSF<br>* FLAG-Ida regimen<br>|
| Placebo Comparator: Placebo<br>Placebo following salvage chemotherapy | Drug: Cytarabine<br>* HAM regimen FLAG-Ida<br>Drug: Mitoxantrone<br>* HAM regimen<br>Drug: Placebo Oral Tablet<br>* Placebo will be administered orally<br>Drug: Fludarabine<br>* FLAG-Ida regimen<br>Drug: Idarubicin<br>* FLAG-Ida regimen<br>Drug: G-CSF<br>* FLAG-Ida regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival (EFS) |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 3 years | 
| Relapse-free Survival (RFS) |  | 3 years | 
| Complete remission rate (CR) |  | 3 years | 
| MRD negative complete remission rate |  | 3 years |