Clinical trial NCT03444649: Epacadostat, Idarubicin and Cytarabine (EIC) in AML
Official title: Epacadostat With Idarubicin and Cytarabine (EIC) for First-line Treatment of AML Patients Fit for Intensive Chemotherapy; a Phase I Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: AML
Keywords: AML
Epacadostat
Idarubicin
Cytarabine
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2018-02-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial assess the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat when added to the anthracycline/cytarabine combination as first-line induction treatment in AML patients fit for intensive treatment

Detailed description: 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 anthracycline/cytarabine combination as first-line induction treatment in 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 18 patients).

Eligibility criteria: Inclusion Criteria:

* AML (according to the 2016 World Health Organization (WHO) classification definition of ≥ 20% blasts; Arber et al, 2016) suitable for intensive treatment (including stem cell transplantation) with a curative intent.
* 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.
* Any previous AML or MDS chemotherapy (with the exception of hydroxyurea/Litalir® for leukocyte control which should be discontinued by the first day of induction chemotherapy
* 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)

Primary outcomes:
measure: Phase 1: Dose finding
timeFrame: 30 days
Secondary outcomes:
measure: Rate of morphologic complete remission (CR)
timeFrame: 60 days
measure: Adverse events
timeFrame: 90 days
measure: Overall survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Berne
country: Switzerland
facility: Departement of Medical Oncology, University Hospital Berne
Study officials:
References: