A Study of APTO-253 in Patients With Relapsed or Refractory AML or MDS

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase Ia/b Dose Escalation and Expansion, Multicenter, Open-label, Safety, Pharmacokinetic and Pharmacodynamic Study of APTO-253 in Patients With Relapsed or Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplasia

Conditions
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Acute Myelogenous Leukemia in Relapse, Acute Myelogenous Leukemia, Relapsed, Adult, Acute Myelogenous Leukemia, Adult, Acute Myelogenous Leukemia, High Risk Myelodysplasia

Intervention / Treatment
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* Drug: APTO-253


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation and Expansion<br>APTO-253 will be given in ascending doses in patients with relapsed or refractory AML or high risk MDS (escalation cohort), until the maximum tolerated dose or recommended dose is reached. Followed by up to 30 patients enrolled in the expansion cohort at the recommended dose. | Drug: APTO-253<br>* APTO-253 will be given in ascending doses starting at 20 mg/m2 until the maximum tolerated dose or recommended dose is reached.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events of APTO-253 | To determine the safety and tolerability of APTO-253 by assessing treatment-related adverse events as assessed by CTCAE v4.0. | Cycle 1 (28 days) | 
| Maximum tolerated dose and dose limiting toxicities | 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. | Cycle 1 (28 days) | 
| Establish recommended dose for future development of APTO-253 | To establish the dose of APTO-253 recommended for future development of APTO-253 for patients with specific types of hematologic malignancies. | Up to 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables including maximum plasma concentration (Cmax) | Pharmacokinetic variables including maximum plasma concentration (Cmax) | Cycle 1 (28 days) | 
| Pharmacokinetic variables including minimum plasma concentration (Cmin) | Pharmacokinetic variables including minimum plasma concentration (Cmin) | Cycle 1 (28 days) | 
| Pharmacokinetic variables including Area Under the Curve (AUC) | Pharmacokinetic variables including Area Under the Curve (AUC) | Cycle 1 (28 days) | 
| Pharmacokinetic variables including volume of distribution | Pharmacokinetic variables including volume of distribution | Cycle 1 (28 days) | 
| Pharmacokinetic variables including clearance | Pharmacokinetic variables including clearance | Cycle 1 (28 days) | 
| Pharmacokinetic variables including serum half-life | Pharmacokinetic variables including serum half-life | Cycle 1 (28 days) | 
| Assess for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS. | To observe patients 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) | 
| Determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect. | To determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect. | Average 2 Cycles (8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, MDS, Leukemia, Acute Myeloid Leukemia, Aptose, APTO-253, Kinase Inhibitor