Epacadostat, Cladribine and Cytarabine (ECC) in AML

NCT ID: NCT03491579

Last Updated: 2018-09-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-31
• Study Completion Date: 2019-10-31

Brief Summary

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

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 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).

Conditions

AML; Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dosis finding

Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with standard chemotherapy (Cladribine and Cytarabine)

Group Type: EXPERIMENTAL

Epacadostat

Intervention Type: DRUG

Epacadostat orally two times daily (BID) for two cycles (28 days each) in combination with standard induction chemotherapy (Cladribine and Cytarabine)

Cladribine

Intervention Type: DRUG

Standard chemotherapy

Cytarabine

Intervention Type: DRUG

Standard chemotherapy

Interventions

Epacadostat

Epacadostat orally two times daily (BID) for two cycles (28 days each) in combination with standard induction chemotherapy (Cladribine and Cytarabine)

Intervention Type: DRUG

Cladribine

Standard chemotherapy

Intervention Type: DRUG

Cytarabine

Standard chemotherapy

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Pabst, Prof

Role: STUDY_CHAIR

Departement of Medical Oncology, University Hospital Berne

Locations

Departement of Medical Oncology, University Hospital Berne

Bern, , Switzerland

Countries

Switzerland

Other Identifiers

ECC

Identifier Type: -

Identifier Source: org_study_id