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

Sponsor
Aptose Biosciences Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02267863
Collaborator
(none)
21
13
1
83
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Study Details

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Oct 1, 2014
Actual Primary Completion Date :
Sep 1, 2021
Actual Study Completion Date :
Sep 1, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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

  1. Pharmacokinetic variables including maximum plasma concentration (Cmax) [Cycle 1 (28 days)]

    Pharmacokinetic variables including maximum plasma concentration (Cmax)

  2. Pharmacokinetic variables including minimum plasma concentration (Cmin) [Cycle 1 (28 days)]

    Pharmacokinetic variables including minimum plasma concentration (Cmin)

  3. Pharmacokinetic variables including Area Under the Curve (AUC) [Cycle 1 (28 days)]

    Pharmacokinetic variables including Area Under the Curve (AUC)

  4. Pharmacokinetic variables including volume of distribution [Cycle 1 (28 days)]

    Pharmacokinetic variables including volume of distribution

  5. Pharmacokinetic variables including clearance [Cycle 1 (28 days)]

    Pharmacokinetic variables including clearance

  6. Pharmacokinetic variables including serum half-life [Cycle 1 (28 days)]

    Pharmacokinetic variables including serum half-life

  7. 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.

  8. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Aptose Biosciences Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Aptose Biosciences Inc.
ClinicalTrials.gov Identifier:
NCT02267863
Other Study ID Numbers:
  • 253-HEM1-01
First Posted:
Oct 20, 2014
Last Update Posted:
Aug 22, 2022
Last Verified:
Aug 1, 2022

Study Results

No Results Posted as of Aug 22, 2022