Acute Myeloid Leukemia
Conditions
Keywords
AML
Brief summary
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.
Interventions
DRUGIdarubicin
Chemotherapy
DRUGCytarabine
Chemotherapy
DRUGIndoximod Freebase
IDO pathway inhibitor
DRUGIndoximod HCL F1
IDO pathway inhibitor
DRUGIndoximod HCL F2
IDO pathway inhibitor
Sponsors
NewLink Genetics Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety assessed by development of RLT, AEs and laboratory parameters of indoximod. | 6 months | Phase 1 |
| Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation. | 6 months | Phase 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of complete response | 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 | — |
| Pharmacokinetics: Serum concentrations (Cmax/Steady State) | 6 months | Characterize the pharmacokinetics (PK) of indoximod, idarubicin and cytarabine through analysis of blood samples |
| Measurable Residual Disease Rate | 2 years | — |
| Clinical response rate | 2 years | — |
| Frequency and severity of adverse events | 2 years | — |
| Event free survival | 2 years | Time on study to induction failure, relapse or death |
Other
| Measure | Time frame | Description |
|---|---|---|
| IDO protein and mRNA expression in diagnostic and follow-up bone marrow aspirate samples | 2 years | — |
| Methylation status of the IDO promoter in diagnostic and follow up bone marrow aspiration samples | 2 years | — |
| IDO expression by immunohistochemistry in diagnostic and follow-up bone marrow biopsy specimens | 2 years | — |
| Serum kynurenine and tryptophan levels | 2 years | Characterize the pharmacodynamic (PD) effect of indoximod |
Countries
United States
Outcome results
None listed