Epacadostat, Idarubicin and Cytarabine (EIC) in AML

Phase 1

Withdrawn

• Conditions: AML
• Interventions: Drug: Epacadostat; Drug: Idarubicin; Drug: Cytarabine; Drug: Daunorubicin

• Registration Number: NCT03444649
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

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).

Study Timeline

• Study First Submitted: 2018-02-19
• Study First Submitted QC: 2018-02-19
• Study First Posted: 2018-02-23
• Status Verified: 2018-09
• Study Start: 2018-09
• Last Update Submitted: 2018-09-07
• Last Update Posted: 2018-09-11
• Primary Completion: 2019-08
• Study Completion: 2019-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dosis finding	Idarubicin	Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with Standard chemotherapy (Idarubicin and Cytarabine)
Dosis finding	Epacadostat	Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with Standard chemotherapy (Idarubicin and Cytarabine)
Dosis finding	Cytarabine	Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with Standard chemotherapy (Idarubicin and Cytarabine)
Dosis finding	Daunorubicin	Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with Standard chemotherapy (Idarubicin and Cytarabine)

Primary Outcome Measures

Name	Time	Method
Phase 1: Dose finding	30 days	To determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat

Secondary Outcome Measures

Name	Time	Method
Overall survival	12 months	Number of patients alive after 12 months
Rate of morphologic complete remission (CR)	60 days	Bone marrow blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0G/L (1000/μL); platelet count \> 100 x G/L (100.000/μL); independence of red cell transfusions.
Adverse events	90 days	Number of patients experiencing toxicity (Adverse Events)

Trial Locations

Locations (1)

Departement of Medical Oncology, University Hospital Berne; 🇨🇭 Berne, Switzerland