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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborators:
GlaxoSmithKline
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01550185
First received: March 7, 2012
Last updated: August 28, 2014
Last verified: August 2014

March 7, 2012
August 28, 2014
May 2012
February 2015   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
MTD and tolerability of eltrombopag olamine in patients with AML [ Time Frame: First 15 days of eltrombopag olamine ] [ Designated as safety issue: Yes ]
Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Complete list of historical versions of study NCT01550185 on ClinicalTrials.gov Archive Site
  • Platelet recovery to >= 100 x 10^9/L and platelet response, assessed based on a modified International Working Group Consensus Criteria for hematologic improvement [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
  • Platelet transfusion requirements [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
Platelet count recovery to >= 100 x 10^9/L [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia
Phase I Dose-Finding Study of Eltrombopag Following High Dose Cytarabine and Mitoxantrone in Relapsed/Refractory Patients With Acute Myeloid Leukemia

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

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Drug: eltrombopag olamine
    Given PO
    Other Names:
    • Promacta
    • SB 497115
    • SB-497115
    • SB497115
  • Procedure: standard follow-up care
    Receive standard care
Experimental: Treatment (eltrombopag olamine)
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.
Interventions:
  • Drug: eltrombopag olamine
  • Procedure: standard follow-up care
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
Not Provided
February 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT01550185
I 206111, NCI-2012-00215
No
Roswell Park Cancer Institute
Roswell Park Cancer Institute
  • National Cancer Institute (NCI)
  • GlaxoSmithKline
Principal Investigator: Wetzler Meir Roswell Park Cancer Institute
Roswell Park Cancer Institute
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP