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

Primary Purpose

Acute Myelogenous Leukemia in Relapse, Acute Myelogenous Leukemia, Relapsed, Adult, Acute Myelogenous Leukemia, Adult

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
APTO-253
Sponsored by
Aptose Biosciences Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia in Relapse focused on measuring AML, MDS, Leukemia, Acute Myeloid Leukemia, Aptose, APTO-253, Kinase Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona Cancer Center
  • UC San Diego Moores Cancer Center
  • University of California, Irvine
  • Emory University; Winship Cancer Institute
  • Ochsner Cancer Institute
  • University of Michigan
  • St. Vincent Frontier Cancer Center
  • University of Rochester; Wilmot Cancer Institute Clinical Trials Office
  • University Hospital
  • Oregon Health & Science University
  • Prisma Health, Institute for Translational Oncology Research
  • Baylor Research Institute
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation and Expansion

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Pharmacokinetic variables including maximum plasma concentration (Cmax)
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Pharmacokinetic variables including Area Under the Curve (AUC)
Pharmacokinetic variables including Area Under the Curve (AUC)
Pharmacokinetic variables including volume of distribution
Pharmacokinetic variables including volume of distribution
Pharmacokinetic variables including clearance
Pharmacokinetic variables including clearance
Pharmacokinetic variables including serum half-life
Pharmacokinetic variables including serum half-life
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.
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.

Full Information

First Posted
October 3, 2014
Last Updated
August 18, 2022
Sponsor
Aptose Biosciences Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02267863
Brief Title
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

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Drug manufacturing process and procedure review
Study Start Date
October 2014 (undefined)
Primary Completion Date
September 2021 (Actual)
Study Completion Date
September 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aptose Biosciences Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation and Expansion
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
APTO-253
Intervention Description
APTO-253 will be given in ascending doses starting at 20 mg/m2 until the maximum tolerated dose or recommended dose is reached.
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events of APTO-253
Description
To determine the safety and tolerability of APTO-253 by assessing treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame
Cycle 1 (28 days)
Title
Maximum tolerated dose and dose limiting toxicities
Description
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.
Time Frame
Cycle 1 (28 days)
Title
Establish recommended dose for future development of APTO-253
Description
To establish the dose of APTO-253 recommended for future development of APTO-253 for patients with specific types of hematologic malignancies.
Time Frame
Up to 7 months
Secondary Outcome Measure Information:
Title
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Description
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Description
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including Area Under the Curve (AUC)
Description
Pharmacokinetic variables including Area Under the Curve (AUC)
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including volume of distribution
Description
Pharmacokinetic variables including volume of distribution
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including clearance
Description
Pharmacokinetic variables including clearance
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including serum half-life
Description
Pharmacokinetic variables including serum half-life
Time Frame
Cycle 1 (28 days)
Title
Assess for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS.
Description
To observe patients for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS.
Time Frame
Average 2 Cycles (8 weeks)
Title
Determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect.
Description
To determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect.
Time Frame
Average 2 Cycles (8 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rafael Bejar, MD., PhD.
Organizational Affiliation
Aptose Biosciences Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0698
Country
United States
Facility Name
University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Emory University; Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Ochsner Cancer Institute
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
St. Vincent Frontier Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59102
Country
United States
Facility Name
University of Rochester; Wilmot Cancer Institute Clinical Trials Office
City
Rochester
State/Province
New York
ZIP/Postal Code
14643
Country
United States
Facility Name
University Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Prisma Health, Institute for Translational Oncology Research
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Baylor Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.aptose.com/clinical-trials/apto-253
Description
Aptose Biosciences

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

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