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

NCT02835729 | Completed Phase 1 DMC

• 1 other identifier: NLG2106
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Measurable Residual Disease Rate

  2 years

• Clinical response rate

  2 years

• Duration of complete response

  2 years

• Event free survival

  2 years

• Cumulative incidence of relapse (CIR)

  2 years

Other Outcomes (4)

• Serum kynurenine and tryptophan levels

  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

Study Arms (2)

Phase 1a

EXPERIMENTAL

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; Drug: Cytarabine; Drug: Indoximod Freebase; Drug: Indoximod HCL F2

Phase 1b (CLOSED TO ACCRUAL)

EXPERIMENTAL

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; Drug: Cytarabine; Drug: Indoximod HCL F1

Interventions

Idarubicin DRUG

Chemotherapy

Phase 1a; Phase 1b (CLOSED TO ACCRUAL)

Cytarabine DRUG

Chemotherapy

Phase 1a; Phase 1b (CLOSED TO ACCRUAL)

Indoximod Freebase DRUG

IDO pathway inhibitor

Phase 1a

Indoximod HCL F1 DRUG

IDO pathway inhibitor

Phase 1b (CLOSED TO ACCRUAL)

Indoximod HCL F2 DRUG

IDO pathway inhibitor

Phase 1a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (2)

Augusta University

Augusta, Georgia, 30912, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2016
• First Posted: July 18, 2016
• Study Start: July 1, 2016
• Primary Completion: October 25, 2019
• Study Completion: December 27, 2019
• Last Updated: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)