Eltrombopag Olamine in Treating Thrombocytopenia in Patients With Chronic Myeloid Leukemia or Myelofibrosis Receiving Tyrosine Kinase Therapy

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT01428635

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

119.7

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II/III trial studies how well eltrombopag olamine works in treating thrombocytopenia in patients with chronic myeloid leukemia or myelofibrosis receiving tyrosine kinase inhibitor therapy. Eltrombopag olamine may cause the body to make platelets after receiving treatment for chronic myeloid leukemia or myelofibrosis.

Condition or Disease	Intervention/Treatment	Phase
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Primary Myelofibrosis Thrombocytopenia	Drug: Eltrombopag Olamine	Phase 2/Phase 3

Detailed Description

PRIMARY OBJECTIVES:

To determine the efficacy of eltrombopag (eltrombopag olamine) for patients with chronic myeloid leukemia (CML) or myelofibrosis (MF) who have developed thrombocytopenia during the course of therapy with tyrosine kinase inhibitors (TKI) as measured by recovery of platelet count.

SECONDARY OBJECTIVES:

To determine the safety of eltrombopag for patients with CML or MF who have developed thrombocytopenia during the course of therapy with TKI.
To determine the dose intensity of TKI after start of therapy with eltrombopag.
To determine response to TKI after start of therapy with eltrombopag.

OUTLINE:

Patients receive eltrombopag olamine orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Eltrombopag for the Management of Thrombocytopenia Associated With Tyrosine Kinase Therapy in Patients With Chronic Myeloid Leukemia (CML) and Myelofibrosis (MF)

Actual Study Start Date :

Jan 13, 2012

Actual Primary Completion Date :

Jan 3, 2022

Actual Study Completion Date :

Jan 3, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Supportive care (eltrombopag olamine) Patients receive eltrombopag olamine PO QD in the absence of disease progression or unacceptable toxicity.	Drug: Eltrombopag Olamine Given PO Other Names: Promacta SB-497115-GR

Arm

Intervention/Treatment

Experimental: Supportive care (eltrombopag olamine)

Patients receive eltrombopag olamine PO QD in the absence of disease progression or unacceptable toxicity.

Drug: Eltrombopag Olamine

Given PO

Other Names:

Promacta

SB-497115-GR

Outcome Measures

Primary Outcome Measures

Efficacy of eltrombopag olamine to increase platelet count as indicated by at least 30% of subjects having a complete (platelet) response: proportions of subjects with complete (platelet) response [Up to 30 days after the last dose of study drug]
The proportions of subjects with complete (platelet) response will be reported together with exact 95% confidence intervals. The denominator will include all subjects who received eltrombopag olamine. Platelet counts over time and in relationship to exposure to eltrombopag and tyrosine kinase inhibitor (TKI) will be summarized using descriptive statistics.

Secondary Outcome Measures

Risk of leukemia defined as suboptimal response and progression to accelerated or blastic phase over time [Up to 30 days after the last dose of study drug]
Kaplan-Meier methods will be used.
Determining the extent of exposure to eltrombopag olamine [Up to 30 days after the last dose of study drug]
Summarized using descriptive statistics. Number of days needed for response and number of days on Eltrombopag
Number of subjects with adverse events, serious adverse events, and adverse events leading to discontinuation, scored using Common Terminology Criteria for Adverse Events version 4.0 [Up to 30 days after the last dose of study drug]
Adverse events will be reported by type, severity and frequency.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

CML patients in chronic phase receiving treatment with any Food and Drug Administration (FDA) approved TKI; or CML patients in accelerated or blastic phase who are considered to be in this phase because of thrombocytopenia or because of clonal evolution and with no other criteria for accelerated/blastic phase or patients with myelofibrosis receiving treatment with FDA approved TKI and with peripheral blood and/or bone marrow blasts =< 10%
Grade >= 3 thrombocytopenia (platelets < 50 x 10^{9/L) after the first 3 months of
therapy with the TKI for patients with CML and platelets < 100 x 10}9/L for patients with MF after the first 3 months of therapy; thrombocytopenia must be either recurrent (i.e., second or greater episode of thrombocytopenia) or having required dose reductions of the TKI
Subject is anticipated to have therapy with TKI continued for >= 3 months
Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for Gilbert's syndrome)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN
Creatinine =< 2 x ULN

Exclusion Criteria:

CML patients in accelerated or blastic phase except for those who are considered to be in this phase because of thrombocytopenia or because of clonal evolution and with no other criteria for accelerated/blastic phase; or myelofibrosis patients who have transformed to acute leukemia or have >= 10% blasts in peripheral blood and/or in bone marrow
Thrombocytopenia that is considered to be unrelated to treatment with TKI or accelerated phase as defined above
Stem cell transplantation within preceding 60 days prior to registration
Patients with documented active hepatitis B or C infection
Patients with known bone marrow reticulin fibrosis (>= grade 2) (only applicable to patients with CML)
Patients with palpable splenomegaly >= 16 cm below coastal margin (only applicable to patients with CML)
Female subjects who are pregnant or breastfeeding
Women of childbearing potential are required to have a beta human chorionic gonadotropin (BHCG) serum or urine pregnancy test performed within 7 days prior to first study drug dose; a female of childbearing potential is a sexually mature woman who:
Has not undergone a hysterectomy or bilateral oophorectomy
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation
Patients with known risk factors for thromboembolism (e.g. Factor V Leiden mutation, antithrombin III (ATIII) deficiency, Protein C and S deficiency, antiphospholipid syndrome, portal hypertension, etc.)