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A Study of Indoximod in Combination With (7+3) Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02835729
Recruitment Status : Recruiting
First Posted : July 18, 2016
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
NewLink Genetics Corporation

Study Description
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Brief Summary:
The purpose of this study is to characterize the regimen limiting toxicities (RLT) and recommended Phase 2 dose (RP2D) of indoximod in patients with newly diagnosed AML receiving remission induction chemotherapy with cytarabine and idarubicin.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Idarubicin Drug: Cytarabine Drug: Indoximod Freebase Drug: Indoximod HCL F1 Drug: Indoximod HCL F2 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study Start Date : July 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : May 2020

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1a

Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (freebase formulation). These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.

All current subjects will transition from indoximod freebase capsules over to indoximod HCL F2 tablets. All new subjects enrolled will also receive indoximod HCL F2 tablets.

 Drug: Idarubicin
Chemotherapy

Drug: Cytarabine
Chemotherapy

Drug: Indoximod Freebase
IDO pathway inhibitor

Drug: Indoximod HCL F2
IDO pathway inhibitor
Experimental: Phase 1b (CLOSED TO ACCRUAL)
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (HCL F1 formulation). These patients will receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
 Drug: Idarubicin
Chemotherapy

Drug: Cytarabine
Chemotherapy

Drug: Indoximod HCL F1
IDO pathway inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. Safety assessed by development of RLT, AEs and laboratory parameters of indoximod. [ Time Frame: 6 months ]
    Phase 1

  2. Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation. [ Time Frame: 6 months ]
    Phase 1


Secondary Outcome Measures :
  1. Measurable Residual Disease Rate [ Time Frame: 2 years ]
  2. Clinical response rate [ Time Frame: 2 years ]
  3. Duration of complete response [ Time Frame: 2 years ]
  4. Event free survival [ Time Frame: 2 years ]
    Time on study to induction failure, relapse or death

  5. Cumulative incidence of relapse (CIR) [ Time Frame: 2 years ]
  6. Overall survival (OS) [ Time Frame: 2 years ]
  7. Proportion of AML patients who become eligible for bone marrow transplantation [ Time Frame: 2 years ]
  8. Frequency and severity of adverse events [ Time Frame: 2 years ]
  9. Pharmacokinetics: Serum concentrations (Cmax/Steady State) [ Time Frame: 6 months ]
    Characterize the pharmacokinetics (PK) of indoximod, idarubicin and cytarabine through analysis of blood samples


Other Outcome Measures:
  1. Serum kynurenine and tryptophan levels [ Time Frame: 2 years ]
    Characterize the pharmacodynamic (PD) effect of indoximod

  2. IDO expression by immunohistochemistry in diagnostic and follow-up bone marrow biopsy specimens [ Time Frame: 2 years ]
  3. IDO protein and mRNA expression in diagnostic and follow-up bone marrow aspirate samples [ Time Frame: 2 years ]
  4. Methylation status of the IDO promoter in diagnostic and follow up bone marrow aspiration samples [ Time Frame: 2 years ]

Eligibility Criteria
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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:

  • A histologically or pathologically confirmed diagnosis of AML based on WHO classification with or without extramedullary disease except for central nervous system disease.
  • ECOG performance status ≤ 2
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • Female patients of childbearing potential must have a negative pregnancy test < 1 week prior to enrollment.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients receiving any other investigational agents or immunotherapy
  • Patients who have received prior chemotherapy for AML with the exception of hydroxyurea or leukapheresis for leukocytosis; prior hypomethylating or immunomodulatory agents for MDS are allowed
  • Previous allo-HSCT of any kind
  • Active, uncontrolled infection including known hepatitis B or C
  • Active autoimmune disease and chronic inflammatory conditions requiring concurrent use of any systemic immunosuppressants or steroids.
  • History of any other active cancer diagnosis
  • Pregnant women
  • Known HIV-infected patients
Contacts and Locations
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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): NCT02835729


Contacts
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Contact: Chris Smith, MS 515-598-5020 ext 2624 csmith@linkp.com

Locations
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United States, Georgia
Augusta University Recruiting
Augusta, Georgia, United States, 30912
Contact: Sandra Wall, RN    706-721-4430    swall@augusta.edu   
Principal Investigator: Vamsi Kota, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Mohammad Imran, M.D.    410-328-2243    mohammad.imran@umm.edu   
Principal Investigator: Ashkan Emadi, M.D., Ph.D.         
Johns Hopkins Withdrawn
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
NewLink Genetics Corporation
More Information
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Responsible Party: NewLink Genetics Corporation
ClinicalTrials.gov Identifier: NCT02835729    
Other Study ID Numbers: NLG2106
First Posted: July 18, 2016    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by NewLink Genetics Corporation:
AML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Tryptophan
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
 Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs