Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01113502
First received: April 28, 2010
Last updated: October 11, 2012
Last verified: October 2012
  Purpose

This is a phase I/II open label study being conducted to evaluate the overall safety and initial effectiveness of an investigational drug, Eltrombopag in patients who are 60 years of age and older and who have Acute Myelogenous Leukemia (AML). Eltrombopag is an investigational drug, which means it has not been approved by the U.S. Food and Drug Administration (FDA) for use in this type of disease. Approximately 35 people will be enrolled on this study at the University of Pennsylvania


Condition Intervention Phase
Male and Female Subjects, Greater Than 60 Years of Age With Non-M3 AML
Drug: Eltrombopag
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I/II Study of Eltrombopag in Elderly Patients With AML

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • Phase I Portion [ Designated as safety issue: No ]
    The maximally tolerated initial starting dose of eltrombopag for elderly subjects with AML. Clinical assessment and laboratory evaluation of Adverse Events and DLTs will be done according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of the National Cancer Institute (NCI) Cancer Therapy Evaluation Program(CTEP).

  • Phase II portion: [ Designated as safety issue: No ]
    The safety and tolerability of eltrombopag in elderly patients with AML at the maximally tolerated starting dose determined in Phase I portion of study. Clinical assessment and laboratory evaluation of Adverse Events and DLTs will be done according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP).


Secondary Outcome Measures:
  • Overall response rate (Phase I and Phase II) [ Designated as safety issue: No ]
    This will include subjects who achieve a complete remission (CR), CR with incomplete count recovery, partial response (PR), and hematologic improvement (HI) based on definitions by the International Working Group (IWG) Of note: subjects who only have HI-platelet (HIp) will not be considered to have had a disease response as this may be due to direct stimulation of meagkaryocytes and not cytotoxic effect

  • Survival, Response and Progression [ Designated as safety issue: No ]

    Overall survival (OS) is defined as the time from first day of therapy to death due to any cause or last patient contact.

    Progression-free survival (PFS) is defined as the time from first day of therapy to disease progression, death due to any cause, or last patient contact.

    PFS is defined for all patients entered on the study, following an intent-to-treat analysis plan.

    Relapse free survival (RFS) Time from complete remission to disease relapse. The time to response is defined as the time from the first day of therapy until the time that measurement criteria are met for response.



Estimated Enrollment: 43
Study Start Date: April 2010
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Detailed Description:

Primary Objectives (Phase I Portion): 1). To determine the safety and tolerability of eltrombopag in elderly subjects with AML 2). To determine the maximally tolerated initial starting dose of eltrombopag for elderly subjects with AML Primary Objectives (Phase II portion): 1). To better define the safety and tolerability of eltrombopag in elderly patients with AML at the maximally tolerated starting dose Page 9 of 18 determined in Phase I portion of study. 2). To determine the incidence of peripheral platelet count improvement (using baseline and response parameters as defined below) for subjects with disease related thrombocytopenia. Secondary Objectives (Phase I and II): 1). To preliminarily determine the efficacy (using AML response criteria as defined below) of eltrombopag in elderly subjects with AML.

2). To perform ex-vivo analyses using subject AML samples and stock eltrombopag to 1) assess leukemic proliferative capacity and 2) investigate potential eltrombopag induced cytoxic mechanisms for leukemic cell death. 3). To perform pharmacodynamic assessments of drug activity in leukemic cells using subject samples collected at various time points before and during drug exposure. 4). To preliminarily correlate pharmacodynamic findings with clinical response.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A diagnosis of non-M3 AML which is either: a). Relapsed after standard chemotherapy or transplant;
  • Newly diagnosed in a patient who is not an appropriate or willing candidate for standard induction chemotherapy - Age equal to or greater than 60 - Platelet count less than 75 - ECOG performance status of 0-2
  • Life expectancy of at least 4 weeks
  • Must be able to consume oral medication
  • Must have recovered from toxic effects of prior chemotherapy
  • Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
  • For Phase I portion only: Subject must be of non-East Asian (Japanese, Chinese, Taiwanese or Korean) descent.
  • For Phase II portion subject can be either East Asian or non-East Asian descent.

Exclusion Criteria:

  • Cytotoxic chemotherapy (including azacitadine or decitabine) within the past 28 days other than hydroxyurea
  • Active participation in any other investigational treatment study for AML.
  • Known HIV or Hepatitis C
  • ECOG performance status greater than 2
  • Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Previous therapy with romiplostim or any other TPO-R agonist
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01113502

Contacts
Contact: Amanda Gordon, RN (215)-663-6392 amanda.gordon@uphs.upenn.edu

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Amanda Gordon, RN    215-663-6392    amanda.gordon@uphs.upenn.edu   
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Noelle Frey, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01113502     History of Changes
Other Study ID Numbers: UPCC 17409
Study First Received: April 28, 2010
Last Updated: October 11, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 20, 2014