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Epacadostat, Cladribine and Cytarabine (ECC) in AML (ECC)

Primary Purpose

AML, Relapse

Status
Withdrawn
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Epacadostat
Cladribine
Cytarabine
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AML focused on measuring AML, Epacadostat, Cladribine, Cytarabine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Departement of Medical Oncology, University Hospital Berne

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dosis finding

Arm Description

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

Outcomes

Primary Outcome Measures

Dose finding
To determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat

Secondary Outcome Measures

Rate of morphologic complete remission (CR)
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
Number of patients experiencing toxicity (Adverse Events)
Overall survival
Number of patients alive after 12 months

Full Information

First Posted
March 31, 2018
Last Updated
September 7, 2018
Sponsor
Insel Gruppe AG, University Hospital Bern
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1. Study Identification

Unique Protocol Identification Number
NCT03491579
Brief Title
Epacadostat, Cladribine and Cytarabine (ECC) in AML
Acronym
ECC
Official Title
Epacadostat With Cladribine and Cytarabine (ECC) in Relapsed / Refractory AML Patients Fit for Intensive Chemotherapy; a Phase I Study.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Withdrawn
Why Stopped
IMP will not be further developed
Study Start Date
December 2018 (Anticipated)
Primary Completion Date
September 2019 (Anticipated)
Study Completion Date
October 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AML, Relapse
Keywords
AML, Epacadostat, Cladribine, Cytarabine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dosis finding
Arm Type
Experimental
Arm Description
Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with standard chemotherapy (Cladribine and Cytarabine)
Intervention Type
Drug
Intervention Name(s)
Epacadostat
Intervention Description
Epacadostat orally two times daily (BID) for two cycles (28 days each) in combination with standard induction chemotherapy (Cladribine and Cytarabine)
Intervention Type
Drug
Intervention Name(s)
Cladribine
Intervention Description
Standard chemotherapy
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Standard chemotherapy
Primary Outcome Measure Information:
Title
Dose finding
Description
To determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Rate of morphologic complete remission (CR)
Description
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.
Time Frame
60 days
Title
Adverse events
Description
Number of patients experiencing toxicity (Adverse Events)
Time Frame
100 days
Title
Overall survival
Description
Number of patients alive after 12 months
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Pabst, Prof
Organizational Affiliation
Departement of Medical Oncology, University Hospital Berne
Official's Role
Study Chair
Facility Information:
Facility Name
Departement of Medical Oncology, University Hospital Berne
City
Berne
ZIP/Postal Code
3010
Country
Switzerland

12. IPD Sharing Statement

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Epacadostat, Cladribine and Cytarabine (ECC) in AML

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