- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01113502
Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)
A Phase I/II Study of Eltrombopag in Elderly Patients With AML
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center of the University of Pennsylvania
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Phase 1 DL1
50 mg; Taken daily by mouth
|
Oral formulation taken daily
Other Names:
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EXPERIMENTAL: Phase 1 DL 2
100 mg; Taken daily by mouth
|
Oral formulation taken daily
Other Names:
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EXPERIMENTAL: Phase 1 DL3
200 mg; Taken daily by mouth
|
Oral formulation taken daily
Other Names:
|
EXPERIMENTAL: Phase 1 DL 4
300 mg; Taken daily by mouth
|
Oral formulation taken daily
Other Names:
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EXPERIMENTAL: Phase 2
200 mg taken daily by mouth for 2 weeks; then 300 mg taken daily by mouth
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Oral formulation taken daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximally Tolerated Dose of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
Time Frame: The time from first day of therapy until subject is off study treatment, an average of 10 weeks.
|
The maximal tolerated dose of eltrombopag for elderly subjects with AML will be defined as the number of dose limiting toxicities per dosing level.
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The time from first day of therapy until subject is off study treatment, an average of 10 weeks.
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Tolerability of Maximum Dose in Phase II Cohort
Time Frame: The time from first day of therapy to the first four weeks of therapy.
|
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).
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The time from first day of therapy to the first four weeks of therapy.
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The Safety of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
Time Frame: First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
|
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.
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First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
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Safety of Eltrombopag in Patients With AML in Phase II Cohort.
Time Frame: First day of study treatment to 30 days after last study treatment, an average of 7 weeks.
|
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.
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First day of study treatment to 30 days after last study treatment, an average of 7 weeks.
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Number of Participants With Peripheral Platelet Count Response in Phase I Cohort
Time Frame: First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
|
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%.
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First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (Phase I and Phase II)
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.
|
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.
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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.
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UPCC 17409
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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