- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03491579
Epacadostat, Cladribine and Cytarabine (ECC) in AML (ECC)
Epacadostat With Cladribine and Cytarabine (ECC) in Relapsed / Refractory AML Patients Fit for Intensive Chemotherapy; a Phase I Study.
Study Overview
Status
Intervention / 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).
Study Type
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Berne, Switzerland, 3010
- Departement of Medical Oncology, University Hospital Berne
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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)
|
Epacadostat orally two times daily (BID) for two cycles (28 days each) in combination with standard induction chemotherapy (Cladribine and Cytarabine)
Standard chemotherapy
Standard chemotherapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose finding
Time Frame: 30 days
|
To determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat
|
30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
60 days
|
Adverse events
Time Frame: 100 days
|
Number of patients experiencing toxicity (Adverse Events)
|
100 days
|
Overall survival
Time Frame: 12 months
|
Number of patients alive after 12 months
|
12 months
|
Collaborators and Investigators
Investigators
- Study Chair: Thomas Pabst, Prof, Departement of Medical Oncology, University Hospital Berne
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Disease Attributes
- Recurrence
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Cytarabine
- Cladribine
Other Study ID Numbers
- ECC
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on AML
-
H Scott BoswellTakedaTerminatedAML | AML, AdultUnited States
-
Technische Universität DresdenAbbVieActive, not recruitingRelapsed Adult AML | Refractory AMLGermany
-
Carbiogene Therapeutics Co. Ltd.Zhejiang Provincial People's HospitalRecruiting
-
Hebei Senlang Biotechnology Inc., Ltd.Recruiting
-
Hebei Senlang Biotechnology Inc., Ltd.Recruiting
-
Institute of Hematology & Blood Diseases Hospital...Recruiting
-
Beijing Immunochina Medical Science & Technology...Completed
-
Stichting Hemato-Oncologie voor Volwassenen NederlandWithdrawn
-
National Research Center for Hematology, RussiaFederal Research Clinical Center of Federal Medical & Biological Agency,... and other collaboratorsRecruiting
Clinical Trials on Epacadostat
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Incyte CorporationTerminated
-
Incyte CorporationTerminatedSolid TumorsUnited States
-
Incyte CorporationCompletedUnresectable or Metastatic Solid TumorsUnited States
-
University of California, DavisCompletedLymphoma | Advanced Solid TumorsUnited States
-
Incyte CorporationGOG Foundation; European Network of Gynaecological Oncological Trial Groups...RecruitingEndometrial CancerUnited States, Belgium, France, Georgia, Greece, Italy, Germany, China
-
National Cancer Institute (NCI)Active, not recruitingStage III Fallopian Tube Cancer AJCC v7 | Stage III Ovarian Cancer AJCC v6 and v7 | Stage III Primary Peritoneal Cancer AJCC v7 | Stage IIIA Fallopian Tube Cancer AJCC v7 | Stage IIIA Ovarian Cancer AJCC v6 and v7 | Stage IIIA Primary Peritoneal Cancer AJCC v7 | Stage IIIB Fallopian Tube Cancer... and other conditionsUnited States
-
Incyte CorporationTerminatedUrothelial CarcinomaUnited States, France, Italy
-
University of ChicagoWithdrawnHead and Neck CancerUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Incyte Corporation; University of VirginiaCompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma | Stage IIIA Skin Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal Melanoma | Recurrent Uveal MelanomaUnited States
-
Incyte CorporationHoffmann-La Roche; Genentech, Inc.TerminatedUC (Urothelial Cancer) | NSCLC (Non-small Cell Lung Carcinoma)United States