Acute Myelogenous Leukemia (AML)Phase 1/2NCT01113502

Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)

A Phase 1/2 study testing Eltrombopag in people with Acute Myelogenous Leukemia (AML), run by Abramson Cancer Center at Penn Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 60 years and older
Conditions the study is for: Acute Myelogenous Leukemia (AML)
What is being tested?: Eltrombopag
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 1 siteUnited States
Study dates: Jun 2010to 10 Nov 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Phase I/II Study of Eltrombopag in Elderly Patients With AML

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

Read the 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.

Conditions: Acute Myelogenous Leukemia (AML)
Being tested: Eltrombopag
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EltrombopagDrug
Also called SB-497115-GR
Oral formulation taken daily

Study groups in NCT01113502
Study group	Role	What they receive
Phase 1 DL1	Experimental	50 mg; Taken daily by mouth Receives: Drug: Eltrombopag
Phase 1 DL 2	Experimental	100 mg; Taken daily by mouth Receives: Drug: Eltrombopag
Phase 1 DL3	Experimental	200 mg; Taken daily by mouth Receives: Drug: Eltrombopag
Phase 1 DL 4	Experimental	300 mg; Taken daily by mouth Receives: Drug: Eltrombopag
Phase 2	Experimental	200 mg taken daily by mouth for 2 weeks; then 300 mg taken daily by mouth Receives: Drug: Eltrombopag

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: The time from first day of therapy until subject is off study treatment, an average of 10 weeks.
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).
Measured: The time from first day of therapy to the first four weeks of therapy.
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.
Measured: First day of study treatment to 30 days after last study treatment, an average of 10 weeks.
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.
Measured: First day of study treatment to 30 days after last study treatment, an average of 7 weeks.
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%.
Measured: First day of study treatment to 30 days after last study treatment, an average of 10 weeks.

Secondary outcomes (1)

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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201010 Nov 2015

First posted30 Apr 2010 (estimated)
Study startJun 2010
Primary completion14 Mar 2013
Study completion10 Nov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute Myelogenous Leukemia (AML)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01113502
Sponsor's protocol ID: UPCC 17409
Status last verified: Jul 2021
First submitted: 28 Apr 2010
Last updated: 5 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of Eltrombopag in Elderly Patients With AML
ClinicalTrials.gov ID: NCT01113502
Acronym / sponsor ID: UPCC 17409
Conditions: Acute Myelogenous Leukemia (AML)
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 44 participants (actual)
Lead sponsor: Abramson Cancer Center at Penn MedicineUniversity, hospital or other
Study start: Jun 2010 (actual)
Primary completion: 14 Mar 2013 (actual)
Study completion: 10 Nov 2015 (actual)
First posted: 30 Apr 2010 (estimated)
Results: Posted 5 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Phase 1 DL1	Experimental	Drug: Eltrombopag50 mg; Taken daily by mouth
Phase 1 DL 2	Experimental	Drug: Eltrombopag100 mg; Taken daily by mouth
Phase 1 DL3	Experimental	Drug: Eltrombopag200 mg; Taken daily by mouth
Phase 1 DL 4	Experimental	Drug: Eltrombopag300 mg; Taken daily by mouth
Phase 2	Experimental	Drug: Eltrombopag200 mg taken daily by mouth for 2 weeks; then 300 mg taken daily by mouth

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EltrombopagAlso: SB-497115-GROral formulation taken daily	Drug	Phase 1 DL 2, Phase 1 DL 4, Phase 1 DL1, Phase 1 DL3, Phase 2

Primary outcome

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.
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).
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.
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.
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%.

1 secondary outcome

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.

Results and safety

Results posted to the registry on 5 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I Dose Level I	4	3
Phase I Dose Level II	3	3
Phase I Dose Level III	7	3
Phase I Dose Level IV	9	6
Phase II Dose Level	21	21

Primary outcome: 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.. Number. Unit: Dose Limiting Toxicities

Measure	Phase I Dose Level I n = 4	Phase I Dose Level II n = 3	Phase I Dose Level III n = 7	Phase I Dose Level IV n = 9
Value	0	0	0	1

Phase I Dose Level I vs Phase I Dose Level II vs Phase I Dose Level III vs Phase I Dose Level IV: Maximum Tolerated Dose (mg): 300

Primary outcome: Tolerability of Maximum Dose in Phase II Cohort

Time frame: The time from first day of therapy to the first four weeks of therapy.. Number. Unit: Dose Limiting toxicities

Measure	Phase II Dose Level n = 21
Value	0

Primary outcome: 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.. Number. Unit: Related Adverse Events

Measure	Phase I Dose Level I n = 4	Phase I Dose Level II n = 3	Phase I Dose Level III n = 7	Phase I Dose Level IV n = 9
Value	1	0	1	6

Primary outcome: 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.. Number. Unit: Number of related Serious Adverse Events

Measure	Phase II Dose Level n = 21
Value	0

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were collected on each subject from the time of treatment initiation until 30 days after the last treatment administration, an average of 14 weeks for the Phase I cohort, and an average of 11 weeks for the Phase II cohort.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I Dose Level I	3 of 4 (75%)	2 of 4 (50%)	2 of 4
Phase I Dose Level II	3 of 3 (100%)	0 of 3 (0%)	1 of 3
Phase I Dose Level III	7 of 7 (100%)	3 of 7 (42.9%)	3 of 7
Phase I Dose Level IV	7 of 9 (77.8%)	5 of 9 (55.6%)	2 of 9
Phase II Dose Level	9 of 21 (42.9%)	0 of 21 (0%)	0 of 21

Limitations and caveats (from the sponsor): Adverse event data for the total counts of the Phase II cohort is available, but the number of individual events per participant in this dosing group is not available. These data have been searched for in all the available reports and materials, requested from the PI, requested from institutional leadership, searched for in institutional clinical trial databases and medical records, but cannot be located.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Noelle Frey, MD principal investigator

Abramson Cancer Center at Penn Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Eltrombopag in people with Acute Myelogenous Leukemia (AML), run by Abramson Cancer Center at Penn Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01113502.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2021.