Pediatric Patients Undergoing Allogeneic Cord Blood Transplantation.
Conditions
Keywords
cord blood transplantation, platelets, eltrombopag
Brief summary
Platelet recovery is significantly hampered following umbilical cord blood transplantation (UCB). Thus, after UCB transplantations, patients are platelet transfusion-dependent for prolong periods of time. Eltrombopag is a thrombopoietin-receptor agonist that initiates thrombopoietin-receptor signaling and thereby induces proliferation and maturation of megakaryocytes. We will evaluate the safety and efficacy of eltrombopag for enhancing platelet engraftment in pediatric patients undergoing cord blood transplantation.
Interventions
DRUGeltrombopag
Children ≥= 40 kg BW: From day +1, start eltrombopag 100 mg/d. If primary end point not reached on day +14, then from day +15 - 150 mg/d. If primary end point not reached on day +28 then from day +29 - 200 mg/d (maximal dose). Children 20-40 kg BW: From day +1, start eltrombopag 50 mg/d. If primary end point not reached on day +14, then from day +15 - 75 mg/d. If primary end point not reached on day +28 then from day +29 - 100 mg/d.If primary end point not reached on day +42, then from day +43 and on - 150 mg/d (maximal dose). Children \< 20 kg BW: From day +1, start eltrombopag - 2 mg/kg/d. If primary end point not reached on day +14, then from day +15 - 3 mg/kg/d. If primary end point not reached on day +28 then from day +29 - 3.5 mg/kg (maximal dose). If present dose not tolerated, return to last tolerated dose. Eltrombopag will be discontinued after platelet count has exceeded 50,000/microliter for 14 consecutive days without administration of platelets.
Sponsors
GlaxoSmithKline
moshe yeshurun
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Patient ≥ 1 year and \< 18 years old. 2. Patients receiving unmanipulated single or double UCB allogeneic grafts. 3. Malignant and non malignant indications for transplantation. 4. Myeloablative and reduced intensity conditioning regimens. 5. Patients must meet all other pre-transplantation criteria of the transplantation center including acceptable tests of heart, liver, kidney, and lung function (standard screening for transplantation per PI, and co-investigators). 6. Written informed must be obtained from the patient's guardian, and accompanying informed assent from the patient for children over 6 years old. 7. Able to comply with study protocol.
Exclusion criteria
1. Indications for transplantation 1. Patients with primary myelofibrosis. 2. French-American-British classification (FAB)M7 acute myeloid leukemia. Acute leukemia secondary to a myeloproliferative neoplasm. 3. Patients with persistent acute leukemia (\>5% bone marrow blasts) at the time of transplantation. 2. Patients with prior thromboembolic event. Patients with previous catheter related thrombosis will be eligible if more than 3 months elapsed. 3. Hypersensitivity to eltrombopag. 4. Liver enzymes abnormalities: Alanine aminotransferase (ALT) levels \> 3 times the upper limit of normal (ULN) or serum bilirubin \> 1.5 ULN (unless due to Gilbert's syndrome or hemolytic bilirubin). \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Platelet engraftment rate up to 50 days post transplantation, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter. | 50 days |
Secondary
| Measure | Time frame |
|---|---|
| Time to partial platelet engraftment, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/microliter. | 180 days |
| Time to sustained complete platelet engraftment defined as the first of 7 consecutive days of an unsupported platelet count of at least 50,000/microliter. | 180 days |
| Complete platelet engraftment rates up to 50 days post transplantation defined as the first of 7 consecutive days of an unsupported platelet count of at least 50,000/microliter. | 50 days |
| Time to neutrophil engraftment defined as the first of 3 consecutive days to achieve an absolute neutrophil count ≥ 500/microliter. | 60 days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Any grade 3/4 adverse event | 12 months | Number of participants with any grade 3/4 adverse event as a measure of safety and tolerability. |
| Thromboembolic events | 12 months | Number of participants with a thromboembolic event as a measure of safety. |
Countries
Israel
Contacts
Primary ContactMoshe Yeshurun, MD
Backup ContactRon Ram, MD
Outcome results
None listed