Eltrombopag in Elderly Acute Myelogenous Leukemia (AML)

NCT01113502 | Terminated Phase 1 Results DMC

• 1 other identifier: UPCC 17409
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Myelogenous Leukemia (AML)

Outcome Measures

Primary Outcomes (5)

• 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.

  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).

  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.

  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.

  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%.

  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)

  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.

Study Arms (5)

Phase 1 DL1

EXPERIMENTAL

50 mg; Taken daily by mouth

Drug: Eltrombopag

Phase 1 DL 2

EXPERIMENTAL

100 mg; Taken daily by mouth

Drug: Eltrombopag

Phase 1 DL3

EXPERIMENTAL

200 mg; Taken daily by mouth

Drug: Eltrombopag

Phase 1 DL 4

EXPERIMENTAL

300 mg; Taken daily by mouth

Drug: Eltrombopag

Phase 2

EXPERIMENTAL

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

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Oral formulation taken daily

Also known as: SB-497115-GR

Phase 1 DL 2; Phase 1 DL 4; Phase 1 DL1; Phase 1 DL3; Phase 2

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Noelle Frey
• Organization: Abramson Cancer Center of the University of Pennsylvania

noelle.frey@pennmedicine.upenn.edu

Study Officials

• Noelle Frey, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2010
• First Posted: April 30, 2010
• Study Start: June 1, 2010
• Primary Completion: March 14, 2013
• Study Completion: November 10, 2015
• Last Updated: August 5, 2021
• Results First Posted: August 5, 2021

Record last verified: 2021-07

Locations

US (1)