Clinical trial NCT02835729: A Study of Indoximod in Combination With (7+3) Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia
Official title: A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: AML
Lead sponsor: Lumos Pharma
Sponsor class: INDUSTRY
First posted: 2016-07-18
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety assessed by development of RLT, AEs and laboratory parameters of indoximod.
timeFrame: 6 months
measure: Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation.
timeFrame: 6 months
Secondary outcomes:
measure: Measurable Residual Disease Rate
timeFrame: 2 years
measure: Clinical response rate
timeFrame: 2 years
measure: Duration of complete response
timeFrame: 2 years
measure: Event free survival
timeFrame: 2 years
measure: Cumulative incidence of relapse (CIR)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Proportion of AML patients who become eligible for bone marrow transplantation
timeFrame: 2 years
measure: Frequency and severity of adverse events
timeFrame: 2 years
measure: Pharmacokinetics: Serum concentrations (Cmax/Steady State)
timeFrame: 6 months
Other outcomes:
measure: Serum kynurenine and tryptophan levels
timeFrame: 2 years
measure: IDO expression by immunohistochemistry in diagnostic and follow-up bone marrow biopsy specimens
timeFrame: 2 years
measure: IDO protein and mRNA expression in diagnostic and follow-up bone marrow aspirate samples
timeFrame: 2 years
measure: Methylation status of the IDO promoter in diagnostic and follow up bone marrow aspiration samples
timeFrame: 2 years
Locations:
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
Study officials:
References: