Eltrombopag Olamine in Increasing Platelet Counts in Patients Undergoing Transplant

Study Overview
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Brief Summary
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This phase II trial studies how well eltrombopag olamine works in increasing platelet counts in patients undergoing transplant. Eltrombopag olamine may help platelet counts and the immune system recover from blood or bone marrow transplant.

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate the rate of platelet engraftment by day 60 in patients undergoing cord blood transplant (CBT) or haploidentical donor stem cell transplantation treated with eltrombopag (eltrombopag olamine). SECONDARY OBJECTIVES: I. To assess safety of eltrombopag in this population. II. To assess neutrophil engraftment with eltrombopag in this population. III. To characterize immune reconstitution. IV. To assess overall survival (OS). V. To assess progression free survival (PFS). VI. To assess incidence of acute graft-versus-host disease (GVHD). OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (CORD BLOOD TRANSPLANT): Patients receive eltrombopag olamine orally (PO) once daily (QD) for 60 days beginning on day -1. ARM II (HAPLOIDENTICAL DONOR STEM CELL TRANSPLANT): Patients receive eltrombopag olamine PO QD for 60 days beginning on day 5. After completion of study treatment, patients are followed up at 1, 2, 3, 6, and 12 months.

Official Title
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Safety and Efficacy of Eltrombopag in Patients Undergoing Cord Blood or Haploidentical Bone Marrow Transplantation

Conditions
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Bone Marrow Transplantation Recipient, Cord Blood Transplant Recipient, Hematopoietic Cell Transplantation Recipient

Intervention / Treatment
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* Drug: Eltrombopag Olamine
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing a cord blood or haploidentical transplantation on any protocol or standard of care treatment plan. Age >/= 18. Females of child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding must be willing to use an effective contraceptive measure until 30 days after the last dose of eltrombopag. Males who have had sexual contact with female of child-bearing potential must be willing to use contraceptive techniques until 30 days after the last dose of eltrombopag. Patient or patient's legal representative(s) is/are able to provide written informed consent to participate. Exclusion Criteria: ALT and AST >/= 2.5 ULN. Serum direct bilirubin >/= 1 mg/dl (except Gilbert's syndrome or hemolysis). Patients of east Asian ancestry (Chinese, Japanese, or Korean Origin). Calculated creatinine clearance < 30ml./min. Creatinine clearance will be calculated using the MDRD method. Arterial or venous thrombosis in the last year except for line-related venous thrombosis more than 3 months ago. Positive beta HCG within 7 days prior to consent in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (cord blood transplant patients)<br>Patients receive eltrombopag olamine PO QD for 60 days beginning on day -1. | Drug: Eltrombopag Olamine<br>* Given PO<br>* Other names: SB-497115-GR;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
| Experimental: Arm II (haploidentical donor stem cell transplant patients)<br>Patients receive eltrombopag olamine PO QD for 60 days beginning on day 5. | Drug: Eltrombopag Olamine<br>* Given PO<br>* Other names: SB-497115-GR;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of platelet engraftment, evaluated as the number of patients experiencing platelet engraftment of greater than 50K/ul | Cumulative incidence will be estimated with death or relapse as a competing risk. Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | Up to day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of platelet engraftment greater than 20K/ul | Cumulative incidence will be estimated with death or relapse as a competing risk. Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | At day 60 | 
| Incidence of platelet engraftment greater than 20K/ul | Cumulative incidence will be estimated with death or relapse as a competing risk. Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | At day 30 | 
| Incidence of platelet engraftment greater than 50K/ul | Cumulative incidence will be estimated with death or relapse as a competing risk. Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | At day 30 | 
| Incidence of neutrophil engraftment defined as the first of three consecutive days that the absolute neutrophil count is greater than 0.5 k/ul | Cumulative incidence will be estimated with death or relapse as a competing risk. Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | Up to day 60 | 
| Time to platelet engraftment | Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | Up to day 60 | 
| Time to neutrophil engraftment | Logistic regression will be used to model the association between engraftment endpoints and covariates of interest. | Up to day 60 | 
| Overall survival | The method of Kaplan and Meier will be used to estimate the distribution of survival time, and distributions will be compared using the log-rank test. Cox proportional hazards regression methods will be used to model survival parameters as a function of disease and demographic covariates of interest. | Up to 1 year | 
| Progression free survival | The method of Kaplan and Meier will be used to estimate the distribution of progression-free survival times, and distributions will be compared using the log-rank test. Cox proportional hazards regression methods will be used to model survival parameters as a function of disease and demographic covariates of interest. | Up to 1 year | 
| Cumulative incidence of acute graft-versus-host disease | The method of Gooley et al will be used to estimate the cumulative incidence of graft-versus-host disease. | Up to day 60 | 
| Cumulative incidence of chronic graft-versus-host disease | The method of Gooley et al will be used to estimate the cumulative incidence of graft-versus-host disease. | Up to 1 year | 
| Incidence of toxicity, assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | The rate of grade 4 and higher non-hematologic toxicity attributable to the drug through day 60 in this trial will be monitored by using the method of Thall, Simon, and Estey. Descriptive summaries of toxicity will be provided by arm and dose. | Up to day 60 |