Acute Myelogenous Leukemia, Acute Myelogenous Leukemia, Adult, Acute Myelogenous Leukemia in Relapse, Acute Myelogenous Leukemia, Relapsed, Adult, High Risk Myelodysplasia
Conditions
Keywords
AML, MDS, Leukemia, Acute Myeloid Leukemia, Aptose, APTO-253, Kinase Inhibitor
Brief summary
This study is being done to evaluate the safety and effectiveness of APTO-253 for the treatment of patients with the condition of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) for which either the standard treatment has failed, is no longer effective, or can no longer be administered safely or poses a risk for your general well being.
Detailed description
This is a multicenter, open-label, Phase Ia/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of APTO-253 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory acute myelogenous leukemia (AML) or high-risk MDS patients. This is to be followed by a cohort expansion phase at the MTD or recommended dose.
Interventions
DRUGAPTO-253
APTO-253 will be given in ascending doses starting at 20 mg/m2 until the maximum tolerated dose or recommended 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
* Patients ≥18 years old * Life expectancy of at least 2 months * Off previous cancer therapy for at least 14 days, or 5 half-lives for noncytotoxic agents prior to first study treatment administration * Patients must have a calculated creatinine clearance \>60 mL/min * Acceptable hematologic, renal and liver functions and coagulation status parameters
Exclusion criteria
* Patients with GVHD requiring systemic immunosuppressive therapy * Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinical significant disease related metabolic disorder * Clinically significant intravascular coagulation * Treatment with other investigational drugs within 14 days prior to first study treatment administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events of APTO-253 | Cycle 1 (28 days) | To determine the safety and tolerability of APTO-253 by assessing treatment-related adverse events as assessed by CTCAE v4.0. |
| Maximum tolerated dose and dose limiting toxicities | Cycle 1 (28 days) | To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of APTO-253 when given on days 1, 8, 15, and 22 of each 28-day cycle. |
| Establish recommended dose for future development of APTO-253 | Up to 7 months | To establish the dose of APTO-253 recommended for future development of APTO-253 for patients with specific types of hematologic malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic variables including volume of distribution | Cycle 1 (28 days) | Pharmacokinetic variables including volume of distribution |
| Pharmacokinetic variables including clearance | Cycle 1 (28 days) | Pharmacokinetic variables including clearance |
| Pharmacokinetic variables including maximum plasma concentration (Cmax) | Cycle 1 (28 days) | Pharmacokinetic variables including maximum plasma concentration (Cmax) |
| Assess for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS. | Average 2 Cycles (8 weeks) | To observe patients for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS. |
| Determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect. | Average 2 Cycles (8 weeks) | To determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect. |
| Pharmacokinetic variables including serum half-life | Cycle 1 (28 days) | Pharmacokinetic variables including serum half-life |
| Pharmacokinetic variables including minimum plasma concentration (Cmin) | Cycle 1 (28 days) | Pharmacokinetic variables including minimum plasma concentration (Cmin) |
| Pharmacokinetic variables including Area Under the Curve (AUC) | Cycle 1 (28 days) | Pharmacokinetic variables including Area Under the Curve (AUC) |
Countries
United States
Outcome results
None listed