Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation

Brief Title

Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation

Official Title

Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation

Brief Summary

      The purpose of this study is to determine whether Eltrombopag may shorten time to platelet
      engraftment after allogeneic cord blood transplantation.
    

Detailed Description

      Platelet recovery is significantly hampered following umbilical cord blood (UCB)
      transplantation. Median time to platelet engraftment (defined as the first of 7 consecutive
      days of an unsupported platelet count of at least 20,000/microliter) in a large retrospective
      study was more than 70 days and cumulative incidence of platelet recovery at 6 months was
      50.5%. In the pediatric population with acute leukemia median time to platelet engraftment
      with UCB transplantation was 59 days and cumulative incidence of platelet recovery at 6
      months was 43%-73%, depending on human leukocyte antigen (HLA) disparity and cell dose.
      Recently, in a cohort of adult patients given myeloablative conditioning followed by double
      UCB transplantation, the cumulative incidence of platelet recovery (≥ 50,000/microliter)at
      100 days was 53%. In another cohort of patients given reduced intensity conditioning regimen
      followed by single or double UCB transplantation, the median time to platelet recovery (≥
      50,000/microliter) and cumulative incidence of platelet recovery at 6 months were 49 days and
      65%, respectively. Thus, after UCB transplantations, patients are platelet
      transfusion-dependent for prolong periods of time, resulting in many drawbacks, such as
      exposure to blood transfusions hazards, higher incidence of platelet allo-reactivity and
      extended periods of bleeding diathesis and undesirable costly and long hospitalizations.

      Eltrombopag is a thrombopoietin-receptor agonist that initiates thrombopoietin-receptor
      signaling and thereby inducing proliferation and maturation of megakaryocytes.Administration
      of eltrombopag increased platelet production in volunteers with normal platelet counts,
      patients with thrombocytopenia secondary to hepatitis C virus infection and in patients with
      chronic immune thrombocytopenic purpura.

      We will evaluate the safety and efficacy of eltrombopag treatment given early after UCB
      transplantation. The study is an open non-comparative study. The primary outcome will be
      cumulative incidence of partial platelet engraftment (first of 7 consecutive days of an
      unsupported platelet count of at least 20,000/microliter)at day 50 post transplantation.
      Secondary objectives are safety, tolerability and other transplantation related outcomes.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Platelet engraftment rate up to 50 days post transplantation, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter.

Secondary Outcome

 Time to partial platelet engraftment, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter.

Condition

Hematological Malignancy

Intervention

Eltrombopag

Study Arms / Comparison Groups

 Eltrombopag
Description:  Eltrombopag will be given orally as a single daily dose. From day +1 after cord blood transplantation, start eltrombopag 100 mg/d. If primary end point not reached on day +14,then from day +15 - 150 mg/d. If primary end point not reached on day +28 then from day +29 - 200 mg/d. If primary end point not reached on day +42 then from day +43 and on - 300 mg/d (maximal dose). If dose not tolerated, return to last tolerated dose.
Eltrombopag will be discontinued after platelet count has exceeded 50,000/microliter for 14 consecutive days without administration of platelets.
In case of decline of platelet count < 30,000/microliter within 15 days from eltrombopag discontinuation, it will be resumed for additional 4 weeks.
After 4 weeks we will re-attempt to hold the drug.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

20

Start Date

January 2013

Completion Date

June 2016

Primary Completion Date

June 2016

Eligibility Criteria

        Inclusion Criteria:

          1. Patient ≥ 18 year old.

          2. Patients receiving unmanipulated single or double umbilical cord blood allogeneic
             grafts.

          3. Malignant and non malignant indications for transplantation.

          4. Myeloablative and reduced intensity conditioning regimens.

          5. Patients must meet all other pre-transplantation criteria of the transplantation
             center including acceptable tests of heart, liver, kidney, and lung function (standard
             screening for transplantation per PI, and co-investigators).

          6. Able to give written informed consent for a clinical trial.

          7. Able to comply with study protocol.

        Exclusion Criteria:

          1. Indications for transplantation

               1. Patients with primary myelofibrosis.

               2. M7 (French-American-British classification) acute myeloid leukemia. Acute
                  leukemia secondary to a myeloproliferative neoplasm.

               3. Patients with persistent acute leukemia (>5% bone marrow blasts) at the time of
                  transplantation.

          2. Patients with prior thromboembolic event. Patients with previous catheter related
             thrombosis will be eligible if more than 3 months elapsed.

          3. Hypersensitivity to eltrombopag.

          4. Liver enzymes abnormalities:

             Alanine transaminase (ALT) levels > 3 times the upper limit of normal (ULN) or serum
             bilirubin > 1.5 ULN (unless due to Gilbert's syndrome or hemolytic bilirubin).

          5. Pregnancy: Women of child-bearing potential and men must agree to use contraception
             prior to study entry and for the duration of study participation. A woman of
             child-bearing potential is defined as a woman who has not been naturally
             post-menopausal for at least 12 consecutive months or with no previous surgical
             sterilization.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Moshe Yeshurun, MD, 972-50-4065543, [email protected]

Location Countries

Israel

Location Countries

Israel

Administrative Informations


NCT ID

NCT01757145

Organization ID

7114


Responsible Party

Sponsor

Study Sponsor

Rabin Medical Center


Study Sponsor

Moshe Yeshurun, MD, Principal Investigator, Rabin Medical Center


Verification Date

February 2013