Thrombocytopenia
Conditions
Keywords
Transplant Thrombocytopenia, Hematopoietic cell transplantation, HCT, Low platelet count, Bleeding, Blood clot, Stem Cell Transplant, Blood And Marrow Transplantation, Eltrombopag, Promacta
Brief summary
The goal of this clinical research study is to learn if eltrombopag can help to improve platelet counts in patients with low platelets after they have had a stem cell transplant. The safety of this drug will also be studied.
Detailed description
The Study Drug: Platelets are cells that help the blood clot. Platelet counts are often lower after receiving a stem cell transplant. When the number of platelets in your body gets too low, it can cause bleeding. Eltrombopag is designed to imitate a protein in your body that helps make platelets. This may help your platelet counts stay normal. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups: * If you are in Group 1, you will receive eltrombopag. * If you are in Group 2, you will receive a placebo. A placebo is a substance that looks like the study drug but has no active ingredients. If you are 1 of the first 20 participants enrolled in this study, you will have an equal chance of being assigned to either group. If you join the study after 20 participants have been enrolled, you will have a better chance of being assigned to Group 1 if eltrombopag has been shown to be more effective. Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving. Study Drug Administration: You will take the study drug/placebo pills by mouth 1 time each day while you are on study. The study drug/placebo should be taken on an empty stomach (1 hour before or 2 hours after food/drink). You may drink water, coffee, and/or tea with the study drug/placebo. You should drink any coffee or tea without milk or cream. The dose of study drug/placebo may be adjusted (raised or lowered) throughout the study based on your reaction to the study drug/placebo. Study Visits: Every 2 weeks, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your weight and vital signs. * You will be asked about any side effects you may have had. * Blood (about 2 tablespoons) will be drawn for routine tests. * Blood (about 1 teaspoon) will be drawn for PK testing. * Blood (about 1 tablespoon) will be drawn to check your immune system. If your blood tests show that you may have fiber deposits (build-up) in the bone marrow, you will have a bone marrow biopsy to check the status of the disease If you have symptoms of cataracts (clouding of the lens of the eye) anytime during the study, you will have an eye exam. Length of Study: You will take the study drug for up to 8 weeks. You will have study visits for 12 weeks. You will be taken off study if you have intolerable side effects. End-of-Treatment Visit: After completion of study drug, you will have the following tests and procedures performed: * You will have a physical exam, including measurement of your weight and vital signs. * You will be asked about any side effects you may have had. * Blood (about 3 tablespoons) will be drawn for routine tests. * Blood (about 1 tablespoon) will be drawn to check your blood's clotting ability. * Blood (about 1 tablespoon) will be drawn to check your immune system. Weeks 10 and 12 (+/- 3 days), you will have the following tests and procedures performed: * You will have a telephone interview. * You will be asked about any side effects you may have had. * Blood (about 3 tablespoons) will be drawn for routine tests. * Blood (about 1 tablespoon) will be drawn to check your blood's clotting ability. * You will either have blood drawn locally or where you live regionally. Within the 3 months after your last dose of study drug, you will have a bone marrow biopsy to check the status of the disease and an eye exam. The eye exam may be performed sooner if you develop symptoms of a cataract, such as blurry vision. This is an investigational study. Eltrombopag is FDA approved and commercially available for the treatment of low platelet counts in patients with idiopathic thrombocytopenic purpura (ITP -- a severe bleeding disease). Its use in patients with low platelet counts after a stem cell transplant is investigational. Up to 64 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGEltrombopag
Starting daily dose 50 mg orally on empty stomach (1 hour before or 2 hours after a meal) for 8 weeks. East Asians start at 25 mg daily.
DRUGPlacebo
Once a day, orally for 8 weeks.
Sponsors
Novartis Pharmaceuticals
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients \>/= 35 days post HCT with Platelet count \</= 20 x 10\^9/l sustained for 7 days or patients are platelet transfusion dependent, and 2. Neutrophil count \>/= 1.5 x 10\^9/l anytime within the last seven days before enrollment. Patients can be on myeloid or erythroid growth factors for example filgrastim), and 3. Age \>/= 18
Exclusion criteria
1. Recurrence or progression of primary malignancy after HCT 2. ALT \>/= 2.5 times the ULN 3. Serum bilirubin \>2mg/dl (unless due to Gilbert's syndrome) 4. Documented deep vein thrombosis within 1 year before enrollment on the study, except if upper arm thrombosis related to central venous catheters, within 3 months before enrollment on the study. 5. ECOG Performance status \>2 6. Pregnancy: Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. A woman of child-bearing potential is defined as a woman who has not been naturally post-menopausal for at least 12 consecutive months or with no previous surgical sterilization. A negative pregnancy test result will be required before any study drug is given.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparing the Efficacy of Eltrombopaq and Placebo | Baseline to Day 57 | Comparison of the efficacy of eltrombopag and placebo in patients with thrombocytopenia post hematopoietic cell transplantation (HCT). |
Countries
United States
Participant flow
Pre-assignment details
Four participants that was enrolled was taken off the study before the randomization process, therefore not included in the participants that started.
Participants by arm
| Arm | Count |
|---|---|
| Eltrombopag Starting dose 50 mg/day orally for 8 weeks
Eltrombopag: Starting daily dose 50 mg orally on empty stomach (1 hour before or 2 hours after a meal) for 8 weeks. East Asians start at 25 mg daily. | 39 |
| Placebo Once a day orally for 8 weeks
Placebo: Once a day, orally for 8 weeks. | 17 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease Progression | 1 | 0 |
| Overall Study | Serious noncompliance | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Eltrombopag | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 14 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 13 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 6 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 | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 28 Participants | 14 Participants | 42 Participants |
| Sex: Female, Male Female | 17 Participants | 6 Participants | 23 Participants |
| Sex: Female, Male Male | 22 Participants | 11 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 39 | 4 / 17 |
| other Total, other adverse events | 31 / 39 | 16 / 17 |
| serious Total, serious adverse events | 14 / 39 | 3 / 17 |
Outcome results
Primary
Comparing the Efficacy of Eltrombopaq and Placebo
Comparison of the efficacy of eltrombopag and placebo in patients with thrombocytopenia post hematopoietic cell transplantation (HCT).
Time frame: Baseline to Day 57
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eltrombopag | Comparing the Efficacy of Eltrombopaq and Placebo | Achieved platelet count >/= 50 x 10 | 9 Participants |
| Eltrombopag | Comparing the Efficacy of Eltrombopaq and Placebo | Achieved platelet count >/= 30 x 10 | 15 Participants |
| Eltrombopag | Comparing the Efficacy of Eltrombopaq and Placebo | Platelet count < 30x 10 | 15 Participants |
| Placebo | Comparing the Efficacy of Eltrombopaq and Placebo | Achieved platelet count >/= 30 x 10 | 5 Participants |
| Placebo | Comparing the Efficacy of Eltrombopaq and Placebo | Achieved platelet count >/= 50 x 10 | 0 Participants |
| Placebo | Comparing the Efficacy of Eltrombopaq and Placebo | Platelet count < 30x 10 | 12 Participants |