A Study of Indoximod in Combination With (7+3) Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to characterize the regimen limiting toxicities (RLT) and recommended Phase 2 dose (RP2D) of indoximod in patients with newly diagnosed AML receiving remission induction chemotherapy with cytarabine and idarubicin.

Official Title
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A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Idarubicin
* Drug: Cytarabine
* Drug: Indoximod Freebase
* Drug: Indoximod HCL F1
* Drug: Indoximod HCL F2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A histologically or pathologically confirmed diagnosis of AML based on WHO classification with or without extramedullary disease except for central nervous system disease. ECOG performance status ≤ 2 Left ventricular ejection fraction (LVEF) ≥ 50% Female patients of childbearing potential must have a negative pregnancy test < 1 week prior to enrollment. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: Patients receiving any other investigational agents or immunotherapy Patients who have received prior chemotherapy for AML with the exception of hydroxyurea or leukapheresis for leukocytosis; prior hypomethylating or immunomodulatory agents for MDS are allowed Previous allo-HSCT of any kind Active, uncontrolled infection including known hepatitis B or C Active autoimmune disease and chronic inflammatory conditions requiring concurrent use of any systemic immunosuppressants or steroids. History of any other active cancer diagnosis Pregnant women Known HIV-infected patients

Ages Eligible for Study
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Minimum Age: 18 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: Phase 1a<br>Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (freebase formulation). These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels. All current subjects will transition from indoximod freebase capsules over to indoximod HCL F2 tablets. All new subjects enrolled will also receive indoximod HCL F2 tablets. | Drug: Idarubicin<br>* Chemotherapy<br>Drug: Cytarabine<br>* Chemotherapy<br>Drug: Indoximod Freebase<br>* IDO pathway inhibitor<br>Drug: Indoximod HCL F2<br>* IDO pathway inhibitor<br>|
| Experimental: Phase 1b (CLOSED TO ACCRUAL)<br>Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (HCL F1 formulation). These patients will receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels. | Drug: Idarubicin<br>* Chemotherapy<br>Drug: Cytarabine<br>* Chemotherapy<br>Drug: Indoximod HCL F1<br>* IDO pathway inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by development of RLT, AEs and laboratory parameters of indoximod. | Phase 1 | 6 months | 
| Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation. | Phase 1 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurable Residual Disease Rate |  | 2 years | 
| Clinical response rate |  | 2 years | 
| Duration of complete response |  | 2 years | 
| Event free survival | Time on study to induction failure, relapse or death | 2 years | 
| Cumulative incidence of relapse (CIR) |  | 2 years | 
| Overall survival (OS) |  | 2 years | 
| Proportion of AML patients who become eligible for bone marrow transplantation |  | 2 years | 
| Frequency and severity of adverse events |  | 2 years | 
| Pharmacokinetics: Serum concentrations (Cmax/Steady State) | Characterize the pharmacokinetics (PK) of indoximod, idarubicin and cytarabine through analysis of blood samples | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML