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

This study is currently recruiting participants.
Verified August 2017 by NewLink Genetics Corporation
Sponsor:
ClinicalTrials.gov Identifier:
NCT02835729
First Posted: July 18, 2016
Last Update Posted: August 3, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
NewLink Genetics Corporation
  Purpose

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.

Safety and tolerability of Indoximod will also be evaluated at the RP2D in combination with standard-of-care (SOC) chemotherapy (defined as induction therapy with idarubicin and cytarabine and consolidation with high-dose cytarabine (HiDAC) in this trial) followed by single agent indoximod maintenance therapy in patients with newly diagnosed AML as compared to safety and tolerability of SOC chemotherapy alone.


Condition Intervention Phase
Acute Myeloid Leukemia Drug: Idarubicin Drug: Cytarabine Drug: Indoximod Other: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b / Randomized Phase 2a Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by NewLink Genetics Corporation:

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

  • Safety and tolerability assessed by development of AEs and laboratory parameters of indoximod + SOC therapy as compared to SOC therapy alone. [ Time Frame: 2 years ]
    Phase 2


Secondary Outcome Measures:
  • Clinical response rate [ Time Frame: 2 years ]
  • Duration of complete response [ Time Frame: 2 years ]
  • Event free survival [ Time Frame: 2 years ]
    Time on study to induction failure, relapse or death

  • Cumulative incidence of relapse (CIR) [ Time Frame: 2 years ]
  • Overall survival (OS) [ Time Frame: 2 years ]
  • Proportion of AML patients who become eligible for bone marrow transplantation [ Time Frame: 2 years ]
  • Frequency and severity of adverse events [ Time Frame: 2 years ]
  • 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:
  • Serum kynurenine and tryptophan levels [ Time Frame: 2 years ]
    Characterize the pharmacodynamic (PD) effect of indoximod

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

Estimated Enrollment: 138
Study Start Date: July 2016
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod. 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.
Drug: Idarubicin
Chemotherapy
Drug: Cytarabine
Chemotherapy
Drug: Indoximod
IDO pathway inhibitor
Experimental: Phase 2 SOC + Indoximod
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod. These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy.
Drug: Idarubicin
Chemotherapy
Drug: Cytarabine
Chemotherapy
Drug: Indoximod
IDO pathway inhibitor
Placebo Comparator: Phase 2 SOC + Placebo
Patients enrolled in this arm will receive standard chemotherapy treatment (7+3) and placebo.
Drug: Idarubicin
Chemotherapy
Drug: Cytarabine
Chemotherapy
Other: Placebo
Placebo

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  • Phase 1:

    • Total bilirubin ≤ 1.5 X institutional upper limit of normal
    • AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal
    • Creatinine Clearance ≥ 60mL/min
  • Phase 2:

    • Total bilirubin ≤ 3 X institutional upper limit of normal
    • AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal
    • Creatinine Clearance ≥ 30mL/min
  • 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
  • Patients with acute promyelocytic leukemia (APL) confirmed with t(15;17)
  • Patients with any history or active central nervous system (CNS) involvement with AML
  • Blastic transformation of chronic myelogenous leukemia (CML)
  • Previous allo-HSCT of any kind
  • Hyperleukocytosis with > 50K blasts/μL.
  • Prior treatment with indoximod
  • Chronic steroid dependence (should have stopped all steroid supplementation 4 weeks prior to enrollment)
  • History of prior treatment with anti-CTLA4 blocking antibody or similar antibodies
  • Active, uncontrolled infection including known hepatitis B or C
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per PI's judgment would limit compliance with study requirements
  • Active autoimmune disease and chronic inflammatory conditions requiring concurrent use of any systemic immunosuppressants or steroids.
  • History of any other active cancer diagnosis (treatment occurring more recently than three years prior) except for surgically resected basal cell carcinoma of the skin or surgically resected Ductal Carcinoma In Situ (DCIS) of the breast
  • Pregnant women
  • Known HIV-infected patients
  • Active gastrointestinal disease causing ongoing malabsorption or obstruction such as, but not limited to, Crohn's disease, celiac sprue, tropical sprue, bowel obstruction, or extensive small bowel resection
  • Unable to take medications by mouth
  • History of allergic reactions attributed to any of the study drugs, compounds of similar chemical or biologic composition, or excipients with these agents
  • Taking strong inhibitors/inducers of CYP3A4, CYP2D6 or CYP2C9
  Contacts and Locations
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
Contact: Chris Smith, MS 515-598-5020 ext 2624 csmith@linkp.com

Locations
United States, Georgia
Augusta University Recruiting
Augusta, Georgia, United States, 30912
Contact: Christine Sanchez, RN    706-721-0660    csanchez@augusta.edu   
Principal Investigator: Jeremy Pantin, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Ashkan Emadi, M.D., Ph.D.         
Johns Hopkins Not yet recruiting
Baltimore, Maryland, United States, 21287
Principal Investigator: B. Douglas Smith, MD         
Sponsors and Collaborators
NewLink Genetics Corporation
  More Information

Responsible Party: NewLink Genetics Corporation
ClinicalTrials.gov Identifier: NCT02835729     History of Changes
Other Study ID Numbers: NLG2106
First Submitted: July 11, 2016
First Posted: July 18, 2016
Last Update Posted: August 3, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by NewLink Genetics Corporation:
AML

Additional relevant MeSH terms:
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