Eltrombopag for Enhancing Platelet Engraftment in Pediatric Patients Undergoing Cord Blood Transplantation

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.

Study Overview

• Status: Unknown
• Conditions: Pediatric Patients Undergoing Allogeneic Cord Blood Transplantation.
• Intervention / Treatment: Drug: eltrombopag

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Recruiting
    • Hadassah Hospital
    • Contact: Michael Shapira, MD; Phone Number: 972-50-7874433
  • Petah Tikva, Israel, 49202
    • Recruiting
    • Schneider Children's Medical Center of Israel
    • Contact: Jerry Stein, MD; Phone Number: 972-50-4057148; Email: jstein@clalit.org.il
    • Principal Investigator: Jerry Stein, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Eltrombopag; Pediatric patients undergoing allogeneic UCB transplantation will receive eltrombopag from day +1 until platelet count has exceeded 50,000/microliter for 14 consecutive days without platelet transfusion. Starting doses are 100 mg/d for children >40 kg body weight (BW), 50 mg/d for children 20-40 kg BW, and 2 mg/kg/d for children <20 kg BW. If unsupported platelet count has not reached the threshold of 20,000/microliter, doses will be escalated every 2 weeks up to maximal doses of 200 mg/d for children ≥ 40 kg BW, 150 mg/d for children 20-40 kg BW and 3.5 mg/kg for children <20 kg BW.

Drug: eltrombopag; 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.; Other Names: Revolade

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any grade 3/4 adverse event	Number of participants with any grade 3/4 adverse event as a measure of safety and tolerability.	12 months
Thromboembolic events	Number of participants with a thromboembolic event as a measure of safety.	12 months

Collaborators and Investigators

• Sponsor: moshe yeshurun
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): June 1, 2016
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: September 8, 2013
• First Submitted That Met QC Criteria: September 8, 2013
• First Posted (Estimate): September 12, 2013

Study Record Updates

• Last Update Posted (Estimate): June 16, 2015
• Last Update Submitted That Met QC Criteria: June 15, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: platelets; eltrombopag; cord blood transplantation
• Other Study ID Numbers: 0195-13