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Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

Primary Purpose

Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
eltrombopag olamine
standard follow-up care
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Basophilic Leukemia

Eligibility Criteria

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

Inclusion Criteria:

  • Relapsed/refractory AML patients who received standard of care cytarabine and mitoxantrone as their chemotherapy regimen
  • Patients must either have Grade 4 thrombocytopenia (platelet counts < 25 x 10^9/L) due to chemotherapy unless transfusion within 24-72 hours
  • Current systemic treatment for AML, with the exception of granulocyte colony-stimulating factor (G-CSF) must have been discontinued at least 7 days prior to entry into the study; in addition:

    • At least 4 weeks before Day 1 for interleukin (IL)-11 (oprelvekin)
    • At least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin
  • Patients with a prior stem cell transplant (SCT) must have failed the SCT
  • Patients must have documented hypoplasia from the bone marrow aspiration and biopsy 14 days +/- 2 days from the initiation of cytarabine treatment schedule (defined as < 5% blasts and < 20% cellularity)
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2
  • Patient is able to understand and comply with protocol requirements and instructions
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) except for Gilbert syndrome or cases clearly not indicative of inadequate organ function, i.e., elevation of indirect (hemolytic) bilirubin in the absence of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormality
  • ALT and AST =< 3 x ULN
  • Creatinine =< 1.5 x ULN
  • Patient is practicing an acceptable method of contraception (documented in chart); female patients (or female partners of male patients) must either be non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use 1 of the following highly effective methods of contraception (i.e., Pearl Index < 1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:

    • Complete abstinence from intercourse
    • Intrauterine device (IUD)
    • Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide)
    • Male partner is sterile prior to entry into the study and is the only partner of the female
    • Systemic contraceptives (combined or progesterone only)
  • Demonstrate the ability to swallow and retain oral medication
  • Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Patients with a diagnosis of acute promyelocytic leukemia
  • Patients with a QTcF > 450 msec (QTcF > 480 msec for patients with Bundle Branch Block)
  • AML patients with persistent disease from the recent treatment defined as > 5% blast and/or > 20% cellularity and reported as persistent residual disease by a pathological report of the patient's bone marrow biopsy 14 days +/- 2 days from the initiation of cytarabine
  • Patients with known thrombophilic risk factors; exception: patients for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
  • Current alcohol or drug abuse
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication
  • Active and uncontrolled infections
  • Patients with known active hepatitis B, hepatitis C, or seropositive human immunodeficiency virus (HIV); testing is not required in the absence of clinical suspicion
  • Patients with liver cirrhosis (as determined by the investigator)
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient that contraindicates the patients' participation
  • Patients of East Asian ancestry (i.e., Chinese, Japanese, Taiwanese, or Korean)
  • Patients with pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] Grade III-IV), or arrhythmia known to increase the risk or thromboembolic events (e.g., atrial fibrillation)
  • Unwilling or unable to follow protocol requirements
  • Any condition which, in the Investigator's opinion, deems the patient an unsuitable candidate to receive study drug
  • No aspirin (ASA) or nonsteroidal antiinflammatory drugs (NSAIDS) administration

Sites / Locations

  • Emory University, Winship Cancer Institute
  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (eltrombopag olamine)

Arm Description

Patients receive eltrombopag olamine PO QD from day 1 up to day 62. Treatment continues for up to 9 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

MTD and tolerability of eltrombopag olamine in patients with AML, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
Platelet count recovery to >= 100 x 10^9/L when eltrombopag olamine is administered following high dose cytarabine and mitoxantrone for the treatment of AML patients

Secondary Outcome Measures

Platelet recovery to >= 100 x 10^9/L and platelet response, assessed based on a modified International Working Group Consensus Criteria for hematologic improvement
Number of platelet transfusions and duration of time without platelet transfusions from the first dose of eltrombopag olamine will be measured.
Platelet response based on a modified International Working Group Consensus Criteria for hematologic improvement
Platelet transfusion requirements

Full Information

First Posted
March 7, 2012
Last Updated
July 20, 2022
Sponsor
Roswell Park Cancer Institute
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01550185
Brief Title
Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia
Official Title
Phase I Dose-Finding Study of Eltrombopag Following High Dose Cytarabine and Mitoxantrone in Relapsed/Refractory Patients With Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Sponsor wanted study rewritten
Study Start Date
May 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to find out the highest safe dose and examine the side effects and effectiveness of eltrombopag olamine in patients with acute myeloid leukemia (AML) treated with chemotherapy that have not responded to previous therapy or have suffered a relapse
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and examine the tolerability of daily oral eltrombopag (eltrombopag olamine) (14 days +/- 2 days after initiation of cytarabine) in patients receiving high dose cytarabine and mitoxantrone for the treatment of acute myeloid leukemia patients with hypoplastic bone marrow 14 days +/- 2 days from initiation of cytarabine. II. To examine platelet count recovery to >= 100 x 10^9/L when eltrombopag is administered following high dose cytarabine and mitoxantrone for the treatment of acute myeloid leukemic patients. OUTLINE: This is a dose-escalation study. Patients receive eltrombopag olamine orally (PO) once daily (QD) from day 1 up to day 62. Treatment continues for up to 9 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (eltrombopag olamine)
Arm Type
Experimental
Arm Description
Patients receive eltrombopag olamine PO QD from day 1 up to day 62. Treatment continues for up to 9 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
eltrombopag olamine
Other Intervention Name(s)
Promacta, SB 497115, SB-497115, SB497115
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
standard follow-up care
Intervention Description
Receive standard care
Primary Outcome Measure Information:
Title
MTD and tolerability of eltrombopag olamine in patients with AML, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
Time Frame
Up to day 15
Title
Platelet count recovery to >= 100 x 10^9/L when eltrombopag olamine is administered following high dose cytarabine and mitoxantrone for the treatment of AML patients
Time Frame
Up to 9 weeks
Secondary Outcome Measure Information:
Title
Platelet recovery to >= 100 x 10^9/L and platelet response, assessed based on a modified International Working Group Consensus Criteria for hematologic improvement
Description
Number of platelet transfusions and duration of time without platelet transfusions from the first dose of eltrombopag olamine will be measured.
Time Frame
Up to 9 weeks
Title
Platelet response based on a modified International Working Group Consensus Criteria for hematologic improvement
Time Frame
Up to 9 weeks
Title
Platelet transfusion requirements
Time Frame
Up to 9 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Relapsed/refractory AML patients who received standard of care cytarabine and mitoxantrone as their chemotherapy regimen Patients must either have Grade 4 thrombocytopenia (platelet counts < 25 x 10^9/L) due to chemotherapy unless transfusion within 24-72 hours Current systemic treatment for AML, with the exception of granulocyte colony-stimulating factor (G-CSF) must have been discontinued at least 7 days prior to entry into the study; in addition: At least 4 weeks before Day 1 for interleukin (IL)-11 (oprelvekin) At least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin Patients with a prior stem cell transplant (SCT) must have failed the SCT Patients must have documented hypoplasia from the bone marrow aspiration and biopsy 14 days +/- 2 days from the initiation of cytarabine treatment schedule (defined as < 5% blasts and < 20% cellularity) Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2 Patient is able to understand and comply with protocol requirements and instructions Total bilirubin =< 1.5 x upper limit of normal (ULN) except for Gilbert syndrome or cases clearly not indicative of inadequate organ function, i.e., elevation of indirect (hemolytic) bilirubin in the absence of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormality ALT and AST =< 3 x ULN Creatinine =< 1.5 x ULN Patient is practicing an acceptable method of contraception (documented in chart); female patients (or female partners of male patients) must either be non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use 1 of the following highly effective methods of contraception (i.e., Pearl Index < 1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study: Complete abstinence from intercourse Intrauterine device (IUD) Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide) Male partner is sterile prior to entry into the study and is the only partner of the female Systemic contraceptives (combined or progesterone only) Demonstrate the ability to swallow and retain oral medication Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Patients with a diagnosis of acute promyelocytic leukemia Patients with a QTcF > 450 msec (QTcF > 480 msec for patients with Bundle Branch Block) AML patients with persistent disease from the recent treatment defined as > 5% blast and/or > 20% cellularity and reported as persistent residual disease by a pathological report of the patient's bone marrow biopsy 14 days +/- 2 days from the initiation of cytarabine Patients with known thrombophilic risk factors; exception: patients for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator Current alcohol or drug abuse Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication Active and uncontrolled infections Patients with known active hepatitis B, hepatitis C, or seropositive human immunodeficiency virus (HIV); testing is not required in the absence of clinical suspicion Patients with liver cirrhosis (as determined by the investigator) Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient that contraindicates the patients' participation Patients of East Asian ancestry (i.e., Chinese, Japanese, Taiwanese, or Korean) Patients with pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] Grade III-IV), or arrhythmia known to increase the risk or thromboembolic events (e.g., atrial fibrillation) Unwilling or unable to follow protocol requirements Any condition which, in the Investigator's opinion, deems the patient an unsuitable candidate to receive study drug No aspirin (ASA) or nonsteroidal antiinflammatory drugs (NSAIDS) administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wetzler Meir
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University, Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States

12. IPD Sharing Statement

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Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

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