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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myelogenous Leukemia; Acute Myelogenous Leukemia in Relapse; Acute Myelogenous Leukemia, Relapsed, Adult; Acute Myelogenous Leukemia, Adult; High Risk Myelodysplasia
• Intervention / Treatment: Drug: APTO-253

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093-0698
      • UC San Diego Moores Cancer Center
    • Orange, California, United States, 92868
      • University of California, Irvine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University; Winship Cancer Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center
  • New York
    • Rochester, New York, United States, 14643
      • University of Rochester; Wilmot Cancer Institute Clinical Trials Office
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health, Institute for Translational Oncology Research
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Research Institute
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion; 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; APTO-253 will be given in ascending doses starting at 20 mg/m2 until the maximum tolerated dose or recommended dose is reached.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Aptose Biosciences Inc.
• Investigators: Study Director: Rafael Bejar, MD., PhD., Aptose Biosciences Inc.

Publications and helpful links

Helpful Links

• Aptose Biosciences

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 20, 2014

Study Record Updates

• Last Update Posted (Actual): August 22, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; Leukemia; MDS; Aptose; Kinase Inhibitor; APTO-253
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: 253-HEM1-01