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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Idarubicin | Drug | Chemotherapy |
| |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Measurable Residual Disease Rate | 2 years | |
| Clinical response rate | 2 years | |
| Duration of complete response |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Augusta University | Augusta | Georgia | 30912 | United States | ||
| University of Maryland |
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| Cytarabine |
| Drug |
Chemotherapy |
|
| Indoximod Freebase | Drug | IDO pathway inhibitor |
|
| Indoximod HCL F1 | Drug | IDO pathway inhibitor |
|
| Indoximod HCL F2 | Drug | IDO pathway inhibitor |
|
| 2 years |
| Event free survival | Time on study to induction failure, relapse or death | 2 years |
| 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) | Characterize the pharmacokinetics (PK) of indoximod, idarubicin and cytarabine through analysis of blood samples | 6 months |
| 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 |
| Baltimore |
| Maryland |
| 21201 |
| United States |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D015255 | Idarubicin |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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