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

Jane Liesveld

Status and phase: Completed; Phase 1

Conditions: Thrombocytopenia; Acute Radiation Syndrome

Treatments: Drug: Eltrombopag

Study type: Interventional

Funder types: Other

Identifiers

NCT00903929

RSRB00028043

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Eltrombopag

Experimental group

Treatment:

Drug: Eltrombopag