Clinical trial NCT02267863: A Study of APTO-253 in Patients With Relapsed or Refractory AML or MDS
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia in Relapse
Acute Myelogenous Leukemia, Relapsed, Adult
Acute Myelogenous Leukemia, Adult
Acute Myelogenous Leukemia
High Risk Myelodysplasia
Keywords: AML
MDS
Leukemia
Acute Myeloid Leukemia
Aptose
APTO-253
Kinase Inhibitor
Lead sponsor: Aptose Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-20
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events of APTO-253
timeFrame: Cycle 1 (28 days)
measure: Maximum tolerated dose and dose limiting toxicities
timeFrame: Cycle 1 (28 days)
measure: Establish recommended dose for future development of APTO-253
timeFrame: Up to 7 months
Secondary outcomes:
measure: Pharmacokinetic variables including maximum plasma concentration (Cmax)
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including minimum plasma concentration (Cmin)
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including Area Under the Curve (AUC)
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including volume of distribution
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including clearance
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including serum half-life
timeFrame: Cycle 1 (28 days)
measure: Assess for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS.
timeFrame: Average 2 Cycles (8 weeks)
measure: Determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect.
timeFrame: Average 2 Cycles (8 weeks)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Atlanta
country: United States
facility: Emory University; Winship Cancer Institute
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Rochester
country: United States
facility: University of Rochester; Wilmot Cancer Institute Clinical Trials Office
state: New York
city: Cleveland
country: United States
facility: University Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Greenville
country: United States
facility: Prisma Health, Institute for Translational Oncology Research
state: South Carolina
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Aptose Biosciences Inc.
name: Rafael Bejar, MD., PhD.
role: STUDY_DIRECTOR
References: