Phase I Study of Eltrombopag for Promoting Thrombopoiesis After Total Body Irradiation
Condition: Thrombocytopenia; Acute Radiation Syndrome
MeSH terms: Thrombocytopenia; Radiation Injuries; Acute Radiation Syndrome
Intervention: Eltrombopag
Intervention description: dose escalation
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Patients who undergo total body irradiation (TBI) for stem cell transplantation have
      prolonged periods of low counts of specific blood cells called platelets. These low platelets
      counts can cause bleeding and infection. Thus far, no drug is available for use to speed the
      recovery of platelets, and therefore transfusions are often necessary.

      The purpose of this study is to test the safety of a drug called eltrombopag in patients who
      have received TBI. The investigators want to find out what effects, good or bad, it has on
      people with low platelet counts due to treatment with TBI. The investigators will also be
      testing how well eltrombopag may work at different doses and determine if this drug speeds up
      the recovery of the platelets.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18

          2. Able to give written informed consent for a clinical trial

          3. Scheduled to undergo an autologous or an allogeneic stem cell transplantation from a
             sibling, related donor, or unrelated donor using a conditioning regimen containing at
             least 400 cGy TBI

          4. Transplantation is being performed for one of the following medical conditions:

               -  Acute myelogenous leukemia

               -  Acute lymphoblastic leukemia

               -  Chronic myelogenous leukemia in chronic, accelerated, or blastic phase

               -  Myelodysplastic syndrome

               -  Myeloproliferative diseases such as chronic myelomonocytic leukemia, agnogeneic
                  myeloid metaplasia with myelofibrosis, polycythemia vera, or essential
                  thrombocythemia

               -  Hodgkin's lymphoma

               -  Non-Hodgkin's lymphoma

               -  Multiple myeloma

               -  Chronic lymphocytic leukemia

               -  Other malignancies or marrow disease such as aplastic anemia where transplant
                  would be appropriate with approval of principal investigator

          5. Patients with therapy-related AML or MDS may be included if their prior malignancy has
             been in remission for at least 12 months. If the remission is less than 12 months,
             approval of the principal investigator is required. Entry could be allowed if the
             malignancy is controlled and not expected to relapse e.g. localized prostate cancer
             treated with XRT.

          6. Patients must meet all other pre-transplantation criteria of the transplant center
             including acceptable tests of heart, liver, kidney, and lung function (Standard
             screening for HSCT per PI, and co-investigators).

          7. Karnofsky performance status must be ≥70%.

        Exclusion Criteria:

          1. TBI dose less than 400 cGY

          2. Cord blood transplantation

          3. HIV infection

          4. Pregnancy or breastfeeding

          5. Creatinine or bilirubin or ALT or AST greater than two times the upper limit of
             normal, unless the abnormal bilirubin is due to Gilbert's syndrome

          6. Active infection requiring systemic antibiotic therapy with antibacterial, antifungal,
             or antiviral agents

          7. Concomitant enrollment in another therapeutic clinical study except with PI approval

          8. Must not have previously received eltrombopag

          9. Patients with moderate or severe liver disease (ALT, AST, or bilirubin ≥ 2X the upper
             limit of normal, unless the abnormal bilirubin is due to Gilbert's syndrome) will be
             excluded

         10. Patients with high risk of thromboembolism based on genetic syndromes , or past
             thromboembolic disease in the past 6 months will be excluded from the study, with the
             exception of those with catheter related clots