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

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Idarubicin
Cytarabine
Indoximod Freebase
Indoximod HCL F1
Indoximod HCL F2
Sponsored by
NewLink Genetics Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Augusta University
  • University of Maryland

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1a

Phase 1b (CLOSED TO ACCRUAL)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety assessed by development of RLT, AEs and laboratory parameters of indoximod.
Phase 1
Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation.
Phase 1

Secondary Outcome Measures

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

Full Information

First Posted
July 11, 2016
Last Updated
June 3, 2020
Sponsor
NewLink Genetics Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02835729
Brief Title
A Study of Indoximod in Combination With (7+3) Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia
Official Title
A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
July 2016 (undefined)
Primary Completion Date
October 25, 2019 (Actual)
Study Completion Date
December 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NewLink Genetics Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1a
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b (CLOSED TO ACCRUAL)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Indoximod Freebase
Intervention Description
IDO pathway inhibitor
Intervention Type
Drug
Intervention Name(s)
Indoximod HCL F1
Intervention Description
IDO pathway inhibitor
Intervention Type
Drug
Intervention Name(s)
Indoximod HCL F2
Intervention Description
IDO pathway inhibitor
Primary Outcome Measure Information:
Title
Safety assessed by development of RLT, AEs and laboratory parameters of indoximod.
Description
Phase 1
Time Frame
6 months
Title
Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation.
Description
Phase 1
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Measurable Residual Disease Rate
Time Frame
2 years
Title
Clinical response rate
Time Frame
2 years
Title
Duration of complete response
Time Frame
2 years
Title
Event free survival
Description
Time on study to induction failure, relapse or death
Time Frame
2 years
Title
Cumulative incidence of relapse (CIR)
Time Frame
2 years
Title
Overall survival (OS)
Time Frame
2 years
Title
Proportion of AML patients who become eligible for bone marrow transplantation
Time Frame
2 years
Title
Frequency and severity of adverse events
Time Frame
2 years
Title
Pharmacokinetics: Serum concentrations (Cmax/Steady State)
Description
Characterize the pharmacokinetics (PK) of indoximod, idarubicin and cytarabine through analysis of blood samples
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Serum kynurenine and tryptophan levels
Description
Characterize the pharmacodynamic (PD) effect of indoximod
Time Frame
2 years
Title
IDO expression by immunohistochemistry in diagnostic and follow-up bone marrow biopsy specimens
Time Frame
2 years
Title
IDO protein and mRNA expression in diagnostic and follow-up bone marrow aspirate samples
Time Frame
2 years
Title
Methylation status of the IDO promoter in diagnostic and follow up bone marrow aspiration samples
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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