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

Phase 1

Completed

• Conditions: Acute Radiation Syndrome; Thrombocytopenia
• Interventions: Drug: Eltrombopag

• Registration Number: NCT00903929
• Lead Sponsor: Jane Liesveld

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-05-15
• Study First Submitted QC: 2009-05-18
• Study First Posted: 2009-05-19
• Study Start: 2009-12
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-04
• Results First Submitted: 2016-04-01
• Results First Submitted QC: 2016-04-01
• Last Update Submitted: 2016-04-01
• Results First Posted: 2016-05-05
• Last Update Posted: 2016-05-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eltrombopag	Eltrombopag	-

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Eltrombopag	1.5 years	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.

Secondary Outcome Measures

Name	Time	Method
Median Number of Platelet Transfusions up to the Day of Engraftment	baseline to day of engraftment
Median Time to Platelet Engraftment	1.5 years	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.