IMP will not be further developed

This trial assess the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat when added to the cladribine/cytarabine chemotherapy in relapsed / refractory AML patients fit for intensive treatment

Background and Rationale:

Epacadostat (INCB024360) is an Inhibitor of Indoleamine 2,3- dioxygenase 1 (IDO1). Indoleamine 2,3- dioxygenase 1 (IDO1) is a 403 amino acid cytosolic haem enzyme encoded by the INDO gene on human chromosome 8p22. IDO1 is responsible for the catabolism of the essential amino acid tryptophan (trp) to kynurenine (kyn) within immune cells and a subset of tumor cells resulting in inhibition of antitumor cell-mediated immune responses. Increased IDO activity correlates with lower CR rates and shorter OS in AML.

Objective:

The primary objective is to determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat when added to the cladribine/cytarabine chemotherapy in relapsed / refractory AML patients fit for intensive treatment

Study Duration:

Phase I part will last from 3 to 18 months (permitting the enrolment of minimum of 3 and a maximum of 24 patients).

Inclusion Criteria:

• Relapsed/refractory AML (according to the 2016 World Health Organization (WHO) classification definition of ≥ 20% blasts; Arber et al, 2016) after at least one line of treatment and suitable for intensive treatment (including stem cell transplantation) without severe concurrent infections.
• Patients must be aged > 18 years, and must have given voluntary written informed consent.
• Women of childbearing potential having a negative serum pregnancy test at screening or at least within 48 hours before start with epacadostat, and willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) during the study and for at least 6 months after the last study drug administration
• Men willing to use an effective contraceptive method (eg, condom, vasectomy) during the study and for at least 6 months after the last study drug administration.

Exclusion Criteria:

• Prior or concurrent malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the subject has been disease-free for more than 6 months.
• APL (acute promyelocytic leukemia) or AML type M3, are excluded from the trial
• Treatment with any investigational product within 4 weeks before the first administration of epacadostat (INCB024360)
• Abnormal organ function if not caused by the underlying disease as considered by the treating physician
• Use of immune-suppressive agents for the past 4 weeks before the first administration of epacadostat (INCB024360). For regular use of systemic corticosteroids, subjects may only be included after stepwise discontinuation to be free of steroids for a minimum of 5 days before the first administration of epacadostat (INCB024360)