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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Rabin Medical Center
Sponsor:
Information provided by (Responsible Party):
Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT01757145
First received: December 6, 2012
Last updated: February 7, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Hematological Malignancy
Bone Marrow Failure Syndrome
Drug: Eltrombopag
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

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. [ Time Frame: 50 days ] [ Designated as safety issue: No ]

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 Frame: 180 days ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to neutrophil engraftment defined as the first of 3 consecutive days to achieve an absolute neutrophil count ≥ 500/microliter. [ Time Frame: 60 days ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Any grade 3/4 adverse event [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Number of participants with any grade 3/4 adverse event as a measure of safety and tolerability.

  • Thromboembolic events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Number of participants with a thromboembolic event as a measure of safety.


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag

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.

Drug: Eltrombopag

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).

Other Name: Revolade

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01757145

Contacts
Contact: Moshe Yeshurun, MD 972-50-4065543 moshey@clalit.org.il
Contact: Ron Ram, MD 972-50-4065621 RonRa@clalit.org.il

Locations
Israel
Davidof Cancer Center, Beilinson hospital, Rabin medical center Recruiting
Petach Tikva, Israel
Contact: Moshe Yeshurun, MD    972-50-4065543    moshey@clalit.org.il   
Principal Investigator: Moshe Yeshurun, MD         
Sponsors and Collaborators
Rabin Medical Center
Investigators
Principal Investigator: Moshe Yeshurun, MD Rabin Medical Center
  More Information

No publications provided

Responsible Party: Rabin Medical Center
ClinicalTrials.gov Identifier: NCT01757145     History of Changes
Other Study ID Numbers: 7114
Study First Received: December 6, 2012
Last Updated: February 7, 2013
Health Authority: Israel: Ethics Commission

Keywords provided by Rabin Medical Center:
Cord blood transplantation
Eltrombopag
Platelet engraftment

Additional relevant MeSH terms:
Pancytopenia
Hemoglobinuria, Paroxysmal
Hematologic Diseases
Anemia, Hemolytic
Anemia
Myelodysplastic Syndromes
Bone Marrow Diseases

ClinicalTrials.gov processed this record on September 22, 2014