Acute Myeloid Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
CG-806, Aptose, FLT3, FLT3-ITD, D835Y, F691L, BTK, C481S, TP53, NRAS, IDH1, BCL2, Gilteritinib, Quizartinib, Midostaurin, Crenolanib, Venetoclax, Ibrutinib, Acalabrutinib, Zanubrutinib, LOXO-305, ARQ 531, AML, Acute Myeloid Leukemia, MDS, Myelodysplastic Syndrome, CLL, Chronic Lymphocytic Leukemia, Resistant, Refractory, Relapsed, Intolerant, Kinase Inhibitor, Non covalent, Luxeptinib
Brief summary
This study is being done to evaluate the safety, tolerability and antitumor activity of oral CG-806 (luxeptinib) for the treatment of patients with Acute Myeloid Leukemia (except APML), secondary AML, therapy-related AML, or higher-risk MDS, whose disease has relapsed, is refractory or who are ineligible for or intolerant of intensive chemotherapy or transplantation.
Detailed description
This is a multicenter, open-label, Phase 1 a/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory Acute Myeloid Leukemia (except APML), secondary AML, therapy-related AML, or higher-risk MDS whose disease has relapsed, is refractory or who are ineligible for or intolerant of intensive chemotherapy or transplantation. This is to be followed by a cohort expansion phase.
Interventions
DRUGCG-806
CG-806 will be given orally in ascending doses starting at 450 mg PO BID until the maximum tolerated dose or candidate recommended Phase 2 dose is reached.
Sponsors
Aptose Biosciences Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥18 years * Life expectancy of at least 3 months * ECOG Performance Status ≤ 2 * Patients must be able to swallow capsules * Adequate hematologic parameters, unless cytopenias are disease caused * Adequate renal, liver and cardiac functions Key
Exclusion criteria
* Patients with GVHD requiring systemic immunosuppressive therapy * Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinically significant disease related metabolic disorder * Clinically significant leukostasis * Treatment with other investigational drugs or receipt of cytotoxic therapy within 14 days prior to first study treatment administration * Receipt of cellular immunotherapeutic agents within 4 weeks prior to first study treatment administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events of CG-806 | At the end of Cycle 1 (each cycle is 28 days) | Patients will be assessed for adverse events during all cycles of treatment and for dose limiting toxicities in Cycle 1 (28-days). Dose escalation to a higher dose level will be considered if none of the first three patients who complete Cycle 1 (28-days) at a given dose level experience a dose limiting toxicity or if only 1 of 6 patients at a given dose level experience a dose-limiting toxicity. |
| Establish a CG-806 dose that maintains a biologically active plasma concentration | At the end of Cycle 1 (each cycle is 28 days) | To determine the dose of CG-806 given orally every 12 hours daily that maintains a biologically active plasma concentration during 28-day cycles. |
| Establish a recommended dose for future development of CG-806 | At the end of Cycle 1 (each cycle is 28 days) | To establish the maximum tolerated dose and/or recommended Phase 2 dose (RP2D) of CG-806 for future clinical trials in patients with AML and other advanced myeloid malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics variables including volume of distribution | At the end of Cycle 1 (each cycle is 28 days) | Pharmacokinetics variables including plasma concentration at various timepoints. |
| Pharmacokinetics variables including clearance | At the end of Cycle 1 (each cycle is 28 days) | Pharmacokinetics variables including plasma concentration at various timepoints. |
| Pharmacokinetics variables including plasma half-life. | At the end of Cycle 1 (each cycle is 28 days) | Pharmacokinetics variables including plasma concentration at various timepoints. |
| To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect. | At the end of Cycle 1 (each cycle is 28 days) | To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect. |
| Pharmacokinetics variables including maximum plasma concentration (Cmax). | At the end of Cycle 1 (each cycle is 28 days) | Pharmacokinetics variables including maximum plasma concentration at various timepoints. |
| To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 patients on Cycle 1 Day -3 compared to Generation 1 formulation of study drug given to patients during Cycle 1. | At the end of Cycle 1 (each cycle is 28 days) | Compare G1 to G3 pharmacokinetics variables including maximum plasma concentration (Cmax) |
| To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 | At the end of Cycle 1 (each cycle is 28 days) | Compare G1 to G3 Pharmacokinetics variables including volume of distribution |
| Compare G1 to G3 Pharmacokinetics variables including clearance | At the end of Cycle 1 (each cycle is 28 days) | Compare G1 to G3 Pharmacokinetics variables including plasma half-life. |
| To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, evaluations | At the end of Cycle 1 (each cycle is 28 days) | To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, and FDG PET-CT imaging evaluations. |
| Pharmacokinetics variables including minimum plasma concentration (Cmin) | At the end of Cycle 1 (each cycle is 28 days) | Pharmacokinetics variables including minimum plasma concentration at various timepoints. |
| Pharmacokinetics variables including area under the curve (AUC) | At the end of Cycle 1 (each cycle is 28 days) | Pharmacokinetics variables including plasma concentration at various timepoints. |
Countries
United States
Outcome results
None listed