A Study of Indoximod in Combination With (7+3) Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia
Phase 1
Completed
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT02835729
- Lead Sponsor
- NewLink Genetics Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1a Indoximod Freebase 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. Phase 1a Indoximod HCL F2 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. Phase 1b (CLOSED TO ACCRUAL) Indoximod HCL F1 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. Phase 1a Idarubicin 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. Phase 1a Cytarabine 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. Phase 1b (CLOSED TO ACCRUAL) Cytarabine 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. Phase 1b (CLOSED TO ACCRUAL) Idarubicin 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Measurable Residual Disease Rate 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
Trial Locations
- Locations (2)
Augusta University
🇺🇸Augusta, Georgia, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States