Clinical trial NCT01113502: Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)
Official title: A Phase I/II Study of Eltrombopag in Elderly Patients With AML
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myelogenous Leukemia (AML)
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2010-04-30
Enrollment: 44
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximally Tolerated Dose of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
timeFrame: The time from first day of therapy until subject is off study treatment, an average of 10 weeks.
measure: Tolerability of Maximum Dose in Phase II Cohort
timeFrame: The time from first day of therapy to the first four weeks of therapy.
measure: The Safety of Eltrombopag for Elderly Subjects With AML in Phase 1 Group
timeFrame: First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
measure: Safety of Eltrombopag in Patients With AML in Phase II Cohort.
timeFrame: First day of study treatment to 30 days after last study treatment, an average of 7 weeks.
measure: Number of Participants With Peripheral Platelet Count Response in Phase I Cohort
timeFrame: First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
Secondary outcomes:
measure: Overall Response Rate (Phase I and Phase II)
timeFrame: 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.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Noelle Frey, MD
role: PRINCIPAL_INVESTIGATOR
References: