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

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

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.

Study Overview

• Status: Completed
• Conditions: Thrombocytopenia; Acute Radiation Syndrome
• Intervention / Treatment: Drug: Eltrombopag

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eltrombopag	Drug: Eltrombopag; dose escalation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jane Liesveld
• Investigators: Principal Investigator: Jane Liesveld, MD, University of Rochester; Study Director: Yuhchyau Chen, MD,PhD, University of Rochester

Publications and helpful links

General Publications

• Liesveld JL, Phillips GL 2nd, Becker M, Constine LS, Friedberg J, Andolina JR, Milner LA, DeBolt J, Smudzin T, Hyrien O, Erickson-Miller CL, Johnson BM, Dawson KL, Chen Y. A phase 1 trial of eltrombopag in patients undergoing stem cell transplantation after total body irradiation. Biol Blood Marrow Transplant. 2013 Dec;19(12):1745-52. doi: 10.1016/j.bbmt.2013.10.002. Epub 2013 Oct 8.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 15, 2009
• First Submitted That Met QC Criteria: May 18, 2009
• First Posted (Estimate): May 19, 2009

Study Record Updates

• Last Update Posted (Estimate): May 5, 2016
• Last Update Submitted That Met QC Criteria: April 1, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Radiation Injuries; Acute Radiation Syndrome
• Other Study ID Numbers: RSRB00028043