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

Phase 1

Terminated

• Conditions: Acute Myelogenous Leukemia, Adult; Acute Myelogenous Leukemia, Relapsed, Adult; Acute Myelogenous Leukemia in Relapse; High Risk Myelodysplasia; Acute Myelogenous Leukemia
• Interventions: Drug: APTO-253

• Registration Number: NCT02267863
• Lead Sponsor: Aptose Biosciences Inc.

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.

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2014-10-03
• Study First Submitted QC: 2014-10-16
• Study First Posted: 2014-10-20
• Primary Completion: 2021-09
• Study Completion: 2021-09
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-18
• Last Update Posted: 2022-08-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation and Expansion	APTO-253	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.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose and dose limiting toxicities	Cycle 1 (28 days)	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.
Incidence of treatment-emergent adverse events of APTO-253	Cycle 1 (28 days)	To determine the safety and tolerability of APTO-253 by assessing treatment-related adverse events as assessed by CTCAE v4.0.
Establish recommended dose for future development of APTO-253	Up to 7 months	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

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

Trial Locations

Locations (13)

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

University of Rochester; Wilmot Cancer Institute Clinical Trials Office; 🇺🇸 Rochester, New York, United States

Ochsner Cancer Institute; 🇺🇸 New Orleans, Louisiana, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

University of California, Irvine; 🇺🇸 Orange, California, United States

Prisma Health, Institute for Translational Oncology Research; 🇺🇸 Greenville, South Carolina, United States

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

St. Vincent Frontier Cancer Center; 🇺🇸 Billings, Montana, United States

Emory University; Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University Hospital; 🇺🇸 Cleveland, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Baylor Research Institute; 🇺🇸 Dallas, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States