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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03491579
Recruitment Status : Withdrawn (IMP will not be further developed)
First Posted : April 9, 2018
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

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

Condition or disease Intervention/treatment Phase
AML Relapse Drug: Epacadostat Drug: Cladribine Drug: Cytarabine Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Epacadostat With Cladribine and Cytarabine (ECC) in Relapsed / Refractory AML Patients Fit for Intensive Chemotherapy; a Phase I Study.
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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)
Drug: Epacadostat
Epacadostat orally two times daily (BID) for two cycles (28 days each) in combination with standard induction chemotherapy (Cladribine and Cytarabine)

Drug: Cladribine
Standard chemotherapy

Drug: Cytarabine
Standard chemotherapy




Primary Outcome Measures :
  1. Dose finding [ Time Frame: 30 days ]
    To determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat


Secondary Outcome Measures :
  1. Rate of morphologic complete remission (CR) [ Time Frame: 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.

  2. Adverse events [ Time Frame: 100 days ]
    Number of patients experiencing toxicity (Adverse Events)

  3. Overall survival [ Time Frame: 12 months ]
    Number of patients alive after 12 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03491579


Locations
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Switzerland
Departement of Medical Oncology, University Hospital Berne
Berne, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
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Study Chair: Thomas Pabst, Prof Departement of Medical Oncology, University Hospital Berne

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03491579    
Other Study ID Numbers: ECC
First Posted: April 9, 2018    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital Inselspital, Berne:
AML
Epacadostat
Cladribine
Cytarabine
Additional relevant MeSH terms:
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Recurrence
Disease Attributes
Pathologic Processes
Cytarabine
Cladribine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs