Clinical Trial: Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Single Arm, Phase II Study of Eltrombopag to Enhance Platelet Count Recovery in Elderly Patients With Acute Myeloid Leukemia Undergoing Remission Induction Therapy

Brief Summary: This phase II trial studies how well eltrombopag olamine works in improving the recovery of platelet counts in older patients with acute myeloid leukemia undergoing induction (the first treatment given for a disease) chemotherapy. Platelet counts recover more slowly in older patients, leading to risk of complications and the delay of post-remission therapy. Eltrombopag olamine may cause the body to make platelets after chemotherapy.

Detailed Summary:

PRIMARY OBJECTIVES:

I.To determine whether eltrombopag leads to early platelet recovery in older AML patients (≥ 60years) who attain morphologic remission on day 14 (range, day 14-17) bone marrow assessment following remission induction chemotherapy (IC).

SECONDARY OBJECTIVES:

I. To determine the effect of eltrombopag on megakaryopoiesis - median time to reach platelet count ≥50,000 /μL and ≥100,000 /μL, number of days of platelet transfusion, rates of platelet transfusion-independence and the median time to reach platelet transfusion independence.

II. To determine the effect of eltrombopag on the rates of clinically significant bleeding events (CSBE).

III. To determine the effect of eltrombopag on erythropoiesis the median time to red blood cell transfusion independence.

IV. To determine the effect of eltrombopag on granulopoiesis- the time taken to reach an absolute neutrophil count of ≥ 500 /μL. V. To determine the safety and tolerability of eltrombopag in AML patients undergoing remission IC - incidence and severity of eltrombopag-related adverse events. VI. To determine rates of complete remission (CR), rates of partial complete remission (CRp), time to attain CR, and time to initiation of postremission consolidation therapy.

OUTLINE:

Patients receive eltrombopag olamine orally (PO) once daily (QD) until platelet counts reach ≥50,000/uL or for 8 weeks, whichever comes earlier. Treatment continues in the absence of unacceptable toxicity.

Same as current

Current Secondary Outcome:

  • Median time needed to reach platelet count >= 50,000 /µL [ Time Frame: up to 12 weeks ]
    Defined as the average number of days from the first day of eltrombopag until the first of five consecutive days with platelet counts >= 50,000 /µL without a platelet transfusion. The time will be summarized using the Kaplan-Meier method and will use the logrank test and proportional hazards models.
  • Number of days of platelet transfusions [ Time Frame: Up to 12 weeks ]
    Defined as the average number of days from the first day of eltrombopag until the patient stopped treatment. The time will be summarized using the Kaplan-Meier method and will use the log-rank test and proportional hazards models.
  • Rates of clinically significant bleeding events [ Time Frame: Up to 12 weeks ]
    The number of bleeding events experienced by patients during treatment including hematuria, gastrointestinal bleed (with or without requiring intervention, retroperitoneal bleeding, intra-cranial bleed, epistaxis not controlled by conservative measures and muscle or soft tissue hematomas.
  • Median time of absolute neutrophil recovery, defined as > 500/uL [ Time Frame: Up to 12 weeks ]
    The average number of days patients take to reach a neutrophil count >500/ul as summarized using the Kaplan-Meier method and modeled using logrank test and proportional hazards.
  • Median rise in hemoglobin level in patients with pretreatment hemoglobin of < 8 g/dL [ Time Frame: Up to 12 weeks ]
    The median increase in hemoglobin levels in g/dL among patients with a starting hemoglobin level <8g/dL
  • Complete Response rate [ Time Frame: Up to 12 weeks ]
    Complete Response rate is defined as the number of patients with a sustained improvement of platelet counts (independent of platelet transfusions) to ≥ 50,000 /µL lasting for at least 2 weeks.
  • Time to attain Complete Response [ Time Frame: Up to 12 weeks ]
    The average number of days patients take to achieve a complete response as defined as a sustained improvement of platelet counts (independent of platelet transfusions) to ≥ 50,000 /µL lasting for at least 2 weeks. This measurement will be summarized using the Kaplan-Meier method and will use the logrank test and proportional hazards models.
  • Partial Complete Response rate [ Time Frame: Up to 12 weeks ]
    Partial complete response rate is defined as the number of patients with a sustained improvement of platelet counts (independent of platelet transfusions) seen by at least a doubling of platelet count from the pretreatment thrombocytopenic level (defined as < 10000 /µL, ) or an absolute increase in platelet counts to between 30000 /µL and 50000 /µL, whichever is higher but not achieving complete response. Or if there is a need to restart eltrombopag due to drop in platelet count to below 50000 /µL following interruption of eltrombopag therapy after achieving platelet counts of > 100000 /µL on the drug.
  • Time to initiation of post-remission therapy [ Time Frame: Up to 12 weeks ]
    The average number of days from the the beginning of treatment to the onset of post-remission therapy as summarized using the Kaplan-Meier method and calculated using the logrank test and proportional hazards models.
  • Rate of refractory or persistent disease [ Time Frame: Up to 12 weeks ]
    The number of patients without complete or partial response to treatment
  • Overall Survival [ Time Frame: Up to 2 years ]
    Survival is defined as the number of days from the day of study registration until the last follow-up or death
  • Incidence of adverse events, determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 4 weeks after last dose of eltrombopag olamine ]


Original Secondary Outcome: Same as current

Information By: Case Comprehensive Cancer Center

Dates:
Date Received: February 24, 2014
Date Started: August 2014
Date Completion: April 2017
Last Updated: October 4, 2016
Last Verified: October 2016