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Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)

Primary Purpose

Acute Myelogenous Leukemia (AML)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Eltrombopag
Sponsored by
Abramson Cancer Center at Penn Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia (AML)

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 azacitidine 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

Sites / Locations

  • Abramson Cancer Center of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1 DL1

Phase 1 DL 2

Phase 1 DL3

Phase 1 DL 4

Phase 2

Arm Description

50 mg; Taken daily by mouth

100 mg; Taken daily by mouth

200 mg; Taken daily by mouth

300 mg; Taken daily by mouth

200 mg taken daily by mouth for 2 weeks; then 300 mg taken daily by mouth

Outcomes

Primary Outcome Measures

Maximally Tolerated Dose of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
The maximal tolerated dose of eltrombopag for elderly subjects with AML will be defined as the number of dose limiting toxicities per dosing level.
Tolerability of Maximum Dose in Phase II Cohort
The tolerability of eltrombopag in elderly patients with AML at the maximally tolerated starting dose determined in Phase I portion of study will be assessed by the number of dose limiting toxicities in the Phase II dosing cohort. 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).
The Safety of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
Safety of eltrombopag will be measured as the number of Grade 3 or higher adverse events per dosing level in Phase 1 group related to Eltrombopag. Relatedness is defined as event being assessed as unlikely, possibly, probably and definitely related to Eltrombopag. All events meeting these assessment categories will be considered related, and those assessed as Grade 3 or higher are reported for each dose level.
Safety of Eltrombopag in Patients With AML in Phase II Cohort.
Safety of eltrombopag will be measured as the number of Serious Adverse Events in Phase II group related to Eltrombopag. Relatedness is defined as event being assessed as unlikely, possibly, probably and definitely related to Eltrombopag. All Serious Adverse Events meeting these assessment categories will be considered related and are reported for the Phase II cohort.
Number of Participants With Peripheral Platelet Count Response in Phase I Cohort
Peripheral platelet count response is defined by number of participants in each dosing cohort exhibiting a peripheral platelet count response using the IWG modified Hematologic Improvement response criteria: For patients with counts less than 100,000/ul: 1) For patients with baseline platelet of > 20,000/ul, absolute increase of platelet count by at least 30,000 /ul 2) For patients with baseline platelets < 20,000/ul, an increase to > 20,000/ul and by at least 100%.

Secondary Outcome Measures

Overall Response Rate (Phase I and Phase II)
This will include subjects who achieve a complete remission (CR) based on definitions by the International Working Group (IWG). CR is defined as the participant have a neutrophil Count>1000/ul, platelet count of >100,000/ul, bone Marrow Blasts < 5% and having no evidence of extramedullary disease.

Full Information

First Posted
April 28, 2010
Last Updated
July 14, 2021
Sponsor
Abramson Cancer Center at Penn Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01113502
Brief Title
Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)
Official Title
A Phase I/II Study of Eltrombopag in Elderly Patients With AML
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Study Start Date
June 2010 (Actual)
Primary Completion Date
March 14, 2013 (Actual)
Study Completion Date
November 10, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia (AML)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 DL1
Arm Type
Experimental
Arm Description
50 mg; Taken daily by mouth
Arm Title
Phase 1 DL 2
Arm Type
Experimental
Arm Description
100 mg; Taken daily by mouth
Arm Title
Phase 1 DL3
Arm Type
Experimental
Arm Description
200 mg; Taken daily by mouth
Arm Title
Phase 1 DL 4
Arm Type
Experimental
Arm Description
300 mg; Taken daily by mouth
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
200 mg taken daily by mouth for 2 weeks; then 300 mg taken daily by mouth
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
SB-497115-GR
Intervention Description
Oral formulation taken daily
Primary Outcome Measure Information:
Title
Maximally Tolerated Dose of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
Description
The maximal tolerated dose of eltrombopag for elderly subjects with AML will be defined as the number of dose limiting toxicities per dosing level.
Time Frame
The time from first day of therapy until subject is off study treatment, an average of 10 weeks.
Title
Tolerability of Maximum Dose in Phase II Cohort
Description
The tolerability of eltrombopag in elderly patients with AML at the maximally tolerated starting dose determined in Phase I portion of study will be assessed by the number of dose limiting toxicities in the Phase II dosing cohort. 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).
Time Frame
The time from first day of therapy to the first four weeks of therapy.
Title
The Safety of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
Description
Safety of eltrombopag will be measured as the number of Grade 3 or higher adverse events per dosing level in Phase 1 group related to Eltrombopag. Relatedness is defined as event being assessed as unlikely, possibly, probably and definitely related to Eltrombopag. All events meeting these assessment categories will be considered related, and those assessed as Grade 3 or higher are reported for each dose level.
Time Frame
First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
Title
Safety of Eltrombopag in Patients With AML in Phase II Cohort.
Description
Safety of eltrombopag will be measured as the number of Serious Adverse Events in Phase II group related to Eltrombopag. Relatedness is defined as event being assessed as unlikely, possibly, probably and definitely related to Eltrombopag. All Serious Adverse Events meeting these assessment categories will be considered related and are reported for the Phase II cohort.
Time Frame
First day of study treatment to 30 days after last study treatment, an average of 7 weeks.
Title
Number of Participants With Peripheral Platelet Count Response in Phase I Cohort
Description
Peripheral platelet count response is defined by number of participants in each dosing cohort exhibiting a peripheral platelet count response using the IWG modified Hematologic Improvement response criteria: For patients with counts less than 100,000/ul: 1) For patients with baseline platelet of > 20,000/ul, absolute increase of platelet count by at least 30,000 /ul 2) For patients with baseline platelets < 20,000/ul, an increase to > 20,000/ul and by at least 100%.
Time Frame
First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
Secondary Outcome Measure Information:
Title
Overall Response Rate (Phase I and Phase II)
Description
This will include subjects who achieve a complete remission (CR) based on definitions by the International Working Group (IWG). CR is defined as the participant have a neutrophil Count>1000/ul, platelet count of >100,000/ul, bone Marrow Blasts < 5% and having no evidence of extramedullary disease.
Time Frame
The time from first day of therapy to time when subject achieves a complete remission (CR), based on the definition of the International Working Group (IWG), approximately 30 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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 azacitidine 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noelle Frey, MD
Organizational Affiliation
Abramson Cancer Center at Penn Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abramson Cancer Center of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)

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