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
Conditions
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.
Detailed 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.
Interventions
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Platelet Response | Up to 9 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Response to TKI Therapy After Eltrombopag | Up to 9 years | (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 \</= 1. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: January 2012 to January 2022
Participants by arm
| Arm | Count |
|---|---|
| Supportive Care (Eltrombopag Olamine) CML Participants Patients receive eltrombopag olamine PO QD in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO | 15 |
| Supportive Care (Eltrombopag Olamine) Myelofibrosis Participants Patients receive eltrombopag olamine PO QD in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO | 6 |
| Total | 21 |
Baseline characteristics
| Characteristic | Supportive Care (Eltrombopag Olamine) Myelofibrosis Participants | Total | Supportive Care (Eltrombopag Olamine) CML Participants |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 8 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 13 Participants | 13 Participants |
| Age, Continuous | 73 years | 57 years | 46 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 19 Participants | 13 Participants |
| Region of Enrollment United States | 6 participants | 21 participants | 15 participants |
| Sex: Female, Male Female | 1 Participants | 9 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 15 | 1 / 6 |
| other Total, other adverse events | 13 / 15 | 4 / 6 |
| serious Total, serious adverse events | 10 / 15 | 4 / 6 |
Outcome results
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.
Time frame: Up to 9 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Eltrombopag Olamine) CML Participants | Number of Participants With a Platelet Response | 12 Participants |
| Supportive Care (Eltrombopag Olamine) Myelofibrosis Participants | Number of Participants With a Platelet Response | 0 Participants |
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 \</= 1.
Time frame: Up to 9 years
Population: Zero participants were analyzed in Myelofibrosis Participants as this outcome measure only analyzes those participants who had a platelet response . Zero participants in the Myelofibrosis group had a platelet response, therefore zero participants in this outcome were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Eltrombopag Olamine) CML Participants | Number of Participants With a Response to TKI Therapy After Eltrombopag | 9 Participants |
| Supportive Care (Eltrombopag Olamine) Myelofibrosis Participants | Number of Participants With a Response to TKI Therapy After Eltrombopag | 0 Participants |