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

Sponsor

NewLink Genetics Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT02835729

Collaborator

(none)

Enrollment

Locations

Arms

41.9

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

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.

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

Study Type:

Interventional

Actual Enrollment :

54 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 :

Jul 1, 2016

Actual Primary Completion Date :

Oct 25, 2019

Actual Study Completion Date :

Dec 27, 2019

Arms and Interventions

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

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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Serum kynurenine and tryptophan levels [2 years]
Characterize the pharmacodynamic (PD) effect of indoximod
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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