Phase I Study of Eltrombopag for Promoting Thrombopoiesis After Total Body Irradiation

Study Overview
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Brief Summary
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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.

Official Title
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Phase I Study of Eltrombopag for Promoting Thrombopoiesis in Patients Undergoing Stem Cell Transplantation After Total Body Irradiation

Conditions
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Thrombocytopenia, Acute Radiation Syndrome

Intervention / Treatment
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* Drug: Eltrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Able to give written informed consent for a clinical trial 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 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 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. 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). Karnofsky performance status must be ≥70%. Exclusion Criteria: TBI dose less than 400 cGY Cord blood transplantation HIV infection Pregnancy or breastfeeding 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 Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents Concomitant enrollment in another therapeutic clinical study except with PI approval Must not have previously received eltrombopag 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eltrombopag<br> | Drug: Eltrombopag<br>* dose escalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Eltrombopag | The MTD was defined as the highest dose if no dose limiting toxicity was observed, or the highest dose at which less than one-third of the patients experienced toxicities not expected in the standard stem cell transplantation setting. | 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Platelet Engraftment | Determined for all participants who completed at least 75% of the planned doses. Platelet engraftment was as defined by the Center for International Blood and Marrow Transplant Research as the first of 3 consecutive days of a platelet count 20,000/mL without platelet trans-fusions for 7 days and/or the first day of a platelet count 100,000/mL without platelet transfusions for 7 days. | 1.5 years | 
| Median Number of Platelet Transfusions up to the Day of Engraftment |  | baseline to day of engraftment |