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

A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: Idarubicin; Drug: Indoximod Freebase; Drug: Indoximod HCL F2; Drug: Indoximod HCL F1

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Cytarabine; Chemotherapy; Drug: Idarubicin; 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: Cytarabine; Chemotherapy; Drug: Idarubicin; Chemotherapy; Drug: Indoximod HCL F1; IDO pathway inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessed by development of RLT, AEs and laboratory parameters of indoximod.	Phase 1	6 months
Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation.	Phase 1	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		2 years
Frequency and severity of adverse events		2 years
Measurable Residual Disease Rate		2 years
Clinical response rate		2 years
Duration of complete response		2 years
Event free survival	Time on study to induction failure, relapse or death	2 years
Cumulative incidence of relapse (CIR)		2 years
Proportion of AML patients who become eligible for bone marrow transplantation		2 years
Pharmacokinetics: Serum concentrations (Cmax/Steady State)	Characterize the pharmacokinetics (PK) of indoximod, idarubicin and cytarabine through analysis of blood samples	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum kynurenine and tryptophan levels	Characterize the pharmacodynamic (PD) effect of indoximod	2 years
IDO expression by immunohistochemistry in diagnostic and follow-up bone marrow biopsy specimens		2 years
IDO protein and mRNA expression in diagnostic and follow-up bone marrow aspirate samples		2 years
Methylation status of the IDO promoter in diagnostic and follow up bone marrow aspiration samples		2 years

Collaborators and Investigators

• Sponsor: NewLink Genetics Corporation

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): October 25, 2019
• Study Completion (Actual): December 27, 2019

Study Registration Dates

• First Submitted: July 11, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimate): July 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antibiotics, Antineoplastic; Cytarabine; Idarubicin; Tryptophan
• Other Study ID Numbers: NLG2106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO