Clinical Trials /

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

NCT01550185

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: I 206111
  • SECONDARY ID: NCI-2012-00215
  • NCT ID: NCT01550185

Conditions

  • 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

Interventions

DrugSynonymsArms
eltrombopag olaminePromacta, SB 497115, SB-497115, SB497115Treatment (eltrombopag olamine)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (eltrombopag olamine)ExperimentalPatients 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.
  • eltrombopag olamine

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Number of platelet transfusions and duration of time without platelet transfusions from the first dose of eltrombopag olamine will be measured.
Measure:Platelet response based on a modified International Working Group Consensus Criteria for hematologic improvement
Time Frame:Up to 9 weeks
Safety Issue:
Description:
Measure:Platelet transfusion requirements
Time Frame:Up to 9 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Roswell Park Cancer Institute

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