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

Thrombocytopenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01428635
• Other study ID #: 2011-0319
• Secondary ID: NCI-2011-0333620
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 13, 2012
• Est. completion date: January 3, 2022

Study information

• Verified date: September 2023
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The goal of this clinical research study is learn if eltrombopag can help control or prevent low platelet counts in patients receiving treatment for CML or myelofibrosis. This is an investigational study. Eltrombopag is FDA approved and commercially available for the treatment of patients with low platelet counts. The use of eltrombopag for the treatment of low platelet counts in patients with CML and myelofibrosis is investigational. Eltrombopag will be provided at no cost to you during the study. If you are found to be eligible to take part in this study, you will receive eltrombopag by mouth 1 time a day. Your dose may be increased every 2 weeks depending on your platelet count response. You should take eltrombopag on an empty stomach. You should not eat for 2 hours before taking eltrombopag. You should wait at least 4 hours between taking eltrombopag and taking other drugs (like antacids), dairy products, juices with calcium added, or supplements containing iron, calcium, aluminum, magnesium, selenium, or zinc. Up to 39 patients will take part in this study. All will be enrolled at MD Anderson. As of June 6, 2017, the study is closed to new participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: January 3, 2022
• Est. primary completion date: January 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Blast Crisis
• Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Primary Myelofibrosis
• Thrombocytopenia

Intervention

Drug:
• Eltrombopag Olamine
Given PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Platelet Response	The primary endpoint is complete (platelet) response (yes/no). A complete (platelet) response will be defined as a sustained (3 months) platelet count of > 50 x 109/L for patients with CML and > 100 x 109/L for patients with MF and at least a 20% increase in platelet count from baseline.	Up to 9 years
Secondary	Number of Participants With a Response to TKI Therapy After Eltrombopag	(CML) : Complete Hematologic Remission : Normalization for 4 weeks of the bone marrow (< 5% blasts) and peripheral blood with WBC within normal institutional limits with no blasts, promyelocytes or myelocytes, and basophils <5%,. Complete cytogenetic response: Ph positive 0%. Partial cytogenetic response: Ph positive 1-35%. Minor cytogenetic response: Ph positive 36-90%. No cytogenetic response: Ph positive 100%. Myelofibrosis : Complete Remission: absence of transfusion or growth factor support: complete resolution of disease-related symptoms/signs including palpable hepatosplenomegaly, hemoglobin > 11 g/dL, platelet count =100 x 10^9/L, absolute neutrophil count = 1.0 x 10^9/L. Normal leukocyte differential with disappearance of nucleated red blood cells and immature myeloid cells in peripheral smear, in the absence of splenectomy. Bone marrow histological remission:presence of age-adjusted normocellularity, < 5% myeloblast , osteomyelofibrosis grade	Up to 9 years

External Links

•   University of Texas MD Anderson Cancer Center Website