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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02267863
Recruitment Status : Terminated (Drug manufacturing process and procedure review)
First Posted : October 20, 2014
Last Update Posted : January 10, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia in Relapse Acute Myelogenous Leukemia, Relapsed, Adult Acute Myelogenous Leukemia, Adult Acute Myelogenous Leukemia High Risk Myelodysplasia Drug: APTO-253 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
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 : October 2014
Actual Primary Completion Date : September 2021
Actual Study Completion Date : September 2021


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.




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events of APTO-253 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Cycle 1 (28 days) ]
    Pharmacokinetic variables including maximum plasma concentration (Cmax)

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

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

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

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

  6. Pharmacokinetic variables including serum half-life [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Average 2 Cycles (8 weeks) ]
    To determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02267863


Locations
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United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093-0698
University of California, Irvine
Orange, California, United States, 92868
United States, Georgia
Emory University; Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Louisiana
Ochsner Cancer Institute
New Orleans, Louisiana, United States, 70121
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Montana
St. Vincent Frontier Cancer Center
Billings, Montana, United States, 59102
United States, New York
University of Rochester; Wilmot Cancer Institute Clinical Trials Office
Rochester, New York, United States, 14643
United States, Ohio
University Hospital
Cleveland, Ohio, United States, 44106
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, South Carolina
Prisma Health, Institute for Translational Oncology Research
Greenville, South Carolina, United States, 29605
United States, Texas
Baylor Research Institute
Dallas, Texas, United States, 75246
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Aptose Biosciences Inc.
Investigators
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Study Director: Rafael Bejar, MD., PhD. Aptose Biosciences Inc.
Additional Information:
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Responsible Party: Aptose Biosciences Inc.
ClinicalTrials.gov Identifier: NCT02267863    
Other Study ID Numbers: 253-HEM1-01
First Posted: October 20, 2014    Key Record Dates
Last Update Posted: January 10, 2022
Last Verified: January 2022
Keywords provided by Aptose Biosciences Inc.:
AML
MDS
Leukemia
Acute Myeloid Leukemia
Aptose
APTO-253
Kinase Inhibitor
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions