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

Primary Purpose

Hematological Malignancy, Bone Marrow Failure Syndrome

Status
Unknown status
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Eltrombopag
Sponsored by
Rabin Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematological Malignancy focused on measuring Cord blood transplantation, Eltrombopag, Platelet engraftment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hadassah hospitalRecruiting
  • Davidof Cancer Center, Beilinson hospital, Rabin medical centerRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eltrombopag

Arm 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.

Outcomes

Primary Outcome Measures

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 Measures

Time to partial platelet engraftment, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter.
Time to sustained complete platelet engraftment defined as the first of 7 consecutive days of an unsupported platelet count of at least 50,000/microliter.
Complete platelet engraftment rates up to 50 days post transplantation defined as the first of 7 consecutive days of an unsupported platelet count of at least 50,000/microliter.
Time to neutrophil engraftment defined as the first of 3 consecutive days to achieve an absolute neutrophil count ≥ 500/microliter.

Full Information

First Posted
December 6, 2012
Last Updated
June 18, 2015
Sponsor
Rabin Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01757145
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Unknown status
Study Start Date
January 2013 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
June 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rabin Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancy, Bone Marrow Failure Syndrome
Keywords
Cord blood transplantation, Eltrombopag, Platelet engraftment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Eltrombopag
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
Revolade
Intervention Description
From day +1, 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 present 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 (if the threshold of platelet count >50,000/microliter will be reached again).
Primary Outcome Measure Information:
Title
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.
Time Frame
50 days
Secondary Outcome Measure Information:
Title
Time to partial platelet engraftment, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter.
Time Frame
180 days
Title
Time to sustained complete platelet engraftment defined as the first of 7 consecutive days of an unsupported platelet count of at least 50,000/microliter.
Time Frame
180 days
Title
Complete platelet engraftment rates up to 50 days post transplantation defined as the first of 7 consecutive days of an unsupported platelet count of at least 50,000/microliter.
Time Frame
50 days
Title
Time to neutrophil engraftment defined as the first of 3 consecutive days to achieve an absolute neutrophil count ≥ 500/microliter.
Time Frame
60 days
Other Pre-specified Outcome Measures:
Title
Any grade 3/4 adverse event
Description
Number of participants with any grade 3/4 adverse event as a measure of safety and tolerability.
Time Frame
12 months
Title
Thromboembolic events
Description
Number of participants with a thromboembolic event as a measure of safety.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient ≥ 18 year old. Patients receiving unmanipulated single or double umbilical cord blood allogeneic grafts. Malignant and non malignant indications for transplantation. Myeloablative and reduced intensity conditioning regimens. 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). Able to give written informed consent for a clinical trial. Able to comply with study protocol. Exclusion Criteria: Indications for transplantation Patients with primary myelofibrosis. M7 (French-American-British classification) acute myeloid leukemia. Acute leukemia secondary to a myeloproliferative neoplasm. Patients with persistent acute leukemia (>5% bone marrow blasts) at the time of transplantation. Patients with prior thromboembolic event. Patients with previous catheter related thrombosis will be eligible if more than 3 months elapsed. Hypersensitivity to eltrombopag. 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). 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Moshe Yeshurun, MD
Phone
972-50-4065543
Email
moshey@clalit.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Ron Ram, MD
Phone
972-50-4065621
Email
RonRa@clalit.org.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Moshe Yeshurun, MD
Organizational Affiliation
Rabin Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hadassah hospital
City
Jerusalem
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Shapira, MD
Phone
972-50-7874433
Facility Name
Davidof Cancer Center, Beilinson hospital, Rabin medical center
City
Petach Tikva
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moshe Yeshurun, MD
Phone
972-50-4065543
Email
moshey@clalit.org.il
First Name & Middle Initial & Last Name & Degree
Moshe Yeshurun, MD

12. IPD Sharing Statement

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

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