Trial of Eltrombopag During Consolidation Therapy in Adults With AML in Complete Remission


About this study

Patients with Acute Myeloid Leukemia (AML) in complete remission will receive eltrombopag while undergoing consolidation chemotherapy with high-dose cytarabine. Eltrombopag may help increase the number of platelets during chemotherapy and may help prevent the risk of bleeding.

Phase I will study the side effects, best dose and platelet effects of eltrombopag when given with consolidation chemotherapy. After the maximum safe and tolerated dose and schedule is found in Phase I, the study will proceed to Phase II. Phase II will confirm the dose and schedule of eltrombopag identified in Phase I that can increase platelet counts in patients receiving consolidation therapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Cytomorphologically documented diagnosis of acute myeloid leukemia (AML). Acute promyelocytic leukemia patients will be excluded (FAB M3). FAB classification, cytogenetics and molecular markers (if applicable) must be available at registration.

Phase I Enrollment:

  • Must be in first or second complete remission, e.g., no evidence of active disease in blood, bone marrow (<5% blasts), or other tissues.
  • For each remission, may have received no more than 2 cycles of induction treatment (any type).
  • May have received no more than one course of consolidation for the current remission prior to enrollment (any type)

Phase II Enrollment:

  • Must be in first complete remission, e.g., no evidence of active disease in blood, bone marrow (<5% blasts), or other tissues.
  • May have received no more than 2 cycles of induction treatment (any type).

Enrollment in Either Phase:

  • Remission status must be documented by a bone marrow examination up to 28 days prior to study registration.
  • Have recovered from induction and first consolidation (if applicable) therapy side effects (or ≤grade 1).
  • ≥18 years of age and ≤70 years of age.
  • ECOG performance status 0, 1, 2.
  • Have not received cytotoxic drug therapy within 21 days of registration.
  • Have not received hematopoietic colony stimulating growth factors within 14 days of registration.
  • Have not received packed red blood cells or platelets within 7 days of registration.
  • Have not received investigational agents within 30 days of registration and will not receive any investigational agents other than eltrombopag/placebo during study.
  • Signed IRB-approved informed consent.
  • Willing to provide blood samples for research purposes.
  • Adequate organ function obtained within 28 days prior to registration:
    • Absolute neutrophil count >1 x 10⁹/L
    • Platelet count >100 x 10⁹/L
    • Total direct serum bilirubin ≤1.5x upper limit of normal (ULN)
    • ALT and AST ≤3x ULN
    • BUN and serum creatinine <2x ULN
    • Albumin ≥2.5 g/dL
    • PT and PTT 80-120% of institutional normal range
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days of registration.
  • Not pregnant nor breast feeding.
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception.
  • Patients of known East Asian ancestry (Chinese, Japanese, Taiwanese, and Korean) are excluded from protocol participation for safety and efficacy reasons.
  • Able to swallow and retain orally administered medication.
  • No clinically significant gastrointestinal abnormalities such as malabsorption syndrome or major resection of the stomach or bowels.
  • No clinical evidence of hepatomegaly or splenomegaly.
  • No known risk for Torsades de Pointes. (Eltrombopag use has not been shown to be associated with Torsades de Pointes.)
  • No active or unresolved infection and must be off all antibiotics for at least 7 days prior to registration.
  • No current evidence of invasive fungal infection.
  • No known Hepatitis B, Hepatitis C active disease.
  • No known Human Immunodeficiency Virus (HIV) seropositivity. The risk for potential toxicities secondary to HIV (e.g., increased risk for fatal opportunistic infection) may confound the toxicity profile of eltrombopag.
  • Patients with a history of Central Nervous System (CNS) leukemia are eligible if there is documentation of no current CNS involvement on cerebrospinal fluid (CSF) examination (e.g., negative CSF by lumbar puncture) within 28 days of registration.
  • No prior or concomitant malignancy in the past 5 years which is currently active and likely to interfere with the patient's treatment for AML or which is likely to increase the patient's morbidity or mortality.
  • No prior chemotherapy or radiation therapy allowed (unless related to AML treatment).
  • No concurrent organ damage or medical problems that would prohibit therapy.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mark Litzow, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office


More information


  • Eltrombopag is a nonpeptidyl thrombopoietin receptor agonist. We evaluated the ex vivo effect of eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndromes (MDSs). At a concentration of 0.1μg/mL, eltrombopag resulted in a significant increase in the number of megakaryocytic colonies in MDS patients and healthy controls compared to baseline. This dose of eltrombopag did not exert any significant change in the proliferation rate or the survival characteristics of patient CD34(+) cells that might clinically imply an unfavorable effect on patients' outcome. These encouraging preclinical data support the rationale of using eltrombopag in the clinic for alleviation of thrombocytopenia in lower risk MDS patients. Read More on PubMed
  • Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, has been shown to increase platelet counts in adults with chronic immune thrombocytopenia and chronic hepatitis C. This multicenter phase 2 study assessed the efficacy and safety of eltrombopag in patients receiving first-line carboplatin/paclitaxel for the treatment of advanced solid tumors. Read More on PubMed
  • Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 microg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag neither led to increased 5-bromo-2-deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xenotransplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients with AML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS. Read More on PubMed
  • Myelosuppression, one of the most common toxicities of chemotherapy, results in varying degree of cytopenias. While neutropenia and anemia have been reduced with the currently approved hematopoietic growth factors, thrombocytopenia remains a significant clinical problem with an unmet medical need. Although platelet transfusions can provide a temporary solution, they do not address the underlying cause of thrombocytopenia. Management of chemotherapy-associated thrombocytopenia often involves dose reductions or treatment delays. Thrombocytopenia can also affect quality of life and significantly increase healthcare costs. With the introduction of several novel antineoplastic agents with an increased propensity to cause thrombocytopenia, a further increase in the incidence of thrombocytopenia can be expected. Despite the extensive efforts in the clinical development of thrombopoietic agents in the past decade, recombinant interleukin-11 (IL-11) is the only agent currently approved by the US Food and Drug Administration for thrombocytopenia induced by chemotherapy. The use of this agent is limited due to its narrow therapeutic index. While promising biologic activity was observed with recombinant thrombopoietins (TPOs) in nonmyeloablative clinical settings, further clinical development was halted due to evidence of neutralizing antibodies to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Recently, a number of novel TPO receptor agonists have been developed with promising clinical activity and a lesser potential for immunogenicity. Several of these second-generation platelet-stimulating agents are currently in clinical development, including peptide (romiplostim, formerly AMG-531) and nonpeptide (eltrombopag and AKR501) mimetics. The clinical trials of romiplostim and eltrombopag are currently ongoing to optimize their dose and schedule in ameliorating chemotherapy-induced thrombocytopenia. Read More on PubMed

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