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

Acute Myelogenous Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02267863
• Other study ID #: 253-HEM1-01
• Status: Terminated
• Phase: Phase 1
• Start date: October 2014
• Est. completion date: September 2021

Study information

• Verified date: August 2022
• Source: Aptose Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: September 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Acute Myelogenous Leukemia in Relapse
• Acute Myelogenous Leukemia, Adult
• Acute Myelogenous Leukemia, Relapsed, Adult
• High Risk Myelodysplasia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University; Winship Cancer Institute	Atlanta	Georgia
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	University Hospital	Cleveland	Ohio
United States	Baylor Research Institute	Dallas	Texas
United States	Prisma Health, Institute for Translational Oncology Research	Greenville	South Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	University of California, Irvine	Orange	California
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Rochester; Wilmot Cancer Institute Clinical Trials Office	Rochester	New York
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Aptose Biosciences Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	Pharmacokinetic variables including maximum plasma concentration (Cmax)	Pharmacokinetic variables including maximum plasma concentration (Cmax)	Cycle 1 (28 days)
Secondary	Pharmacokinetic variables including minimum plasma concentration (Cmin)	Pharmacokinetic variables including minimum plasma concentration (Cmin)	Cycle 1 (28 days)
Secondary	Pharmacokinetic variables including Area Under the Curve (AUC)	Pharmacokinetic variables including Area Under the Curve (AUC)	Cycle 1 (28 days)
Secondary	Pharmacokinetic variables including volume of distribution	Pharmacokinetic variables including volume of distribution	Cycle 1 (28 days)
Secondary	Pharmacokinetic variables including clearance	Pharmacokinetic variables including clearance	Cycle 1 (28 days)
Secondary	Pharmacokinetic variables including serum half-life	Pharmacokinetic variables including serum half-life	Cycle 1 (28 days)
Secondary	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)
Secondary	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)

External Links

•   Aptose Biosciences