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

• ClinicalTrials.gov Identifier: NCT00903929
• Recruitment Status: Completed
• First Posted: May 19, 2009
• Results First Posted: May 5, 2016
• Last Update Posted: May 5, 2016
• Sponsor: Jane Liesveld
• Information provided by (Responsible Party): Jane Liesveld, University of Rochester

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Thrombocytopenia; Acute Radiation Syndrome	Drug: Eltrombopag	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of Eltrombopag for Promoting Thrombopoiesis in Patients Undergoing Stem Cell Transplantation After Total Body Irradiation
• Study Start Date: December 2009
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eltrombopag	Drug: Eltrombopag; dose escalation

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose (MTD) of Eltrombopag [ Time Frame: 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 :

1. Median Time to Platelet Engraftment [ Time Frame: 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.
2. Median Number of Platelet Transfusions up to the Day of Engraftment [ Time Frame: baseline to day of engraftment ]

Eligibility Criteria

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

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

Contacts and Locations

Sponsors and Collaborators

Jane Liesveld

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jane Liesveld, Professor M&D-Hematology/Oncology, University of Rochester
• ClinicalTrials.gov Identifier: NCT00903929
• Other Study ID Numbers: RSRB00028043
• First Posted: May 19, 2009
• Results First Posted: May 5, 2016
• Last Update Posted: May 5, 2016
• Last Verified: April 2016

Additional relevant MeSH terms:

Thrombocytopenia; Radiation Injuries; Acute Radiation Syndrome; Blood Platelet Disorders; Hematologic Diseases; Wounds and Injuries