A Phase II Dose-escalation Study Characterizing the PK of Eltrombopag in Pediatric Patients With Previously Untreated or Relapsed Severe Aplastic Anemia or Recurrent Aplastic Anemia



Status:Recruiting
Conditions:Anemia
Therapuetic Areas:Hematology
Healthy:No
Age Range:1 - 18
Updated:3/30/2019
Start Date:September 30, 2017
End Date:April 1, 2024
Contact:Novartis Pharmaceuticals
Email:novartis.email@novartis.com
Phone:1-888-669-6682

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A Phase II, Open-label, Non-controlled, Intra-patient Dose-escalation Study to Characterize the Pharmacokinetics After Oral Administration of Eltrombopag in Pediatric Patients With Refractory, Relapsed or Treatment Naive Severe Aplastic Anemia or Recurrent Aplastic Anemia

This is a phase II, open label, multi-center, intra-patient dose escalation study to
characterize the pharmacokinetics after oral administration of eltrombopag in combination
with immunosuppressive therapy in pediatric patients with previously untreated or
relapsed/refractory severe aplastic anemia or recurrent aplastic anemia.

All patients will be treated with eltrombopag for the 26-week Treatment Period, followed by a
52-week Follow-Up Period. Patients who have been previously untreated with immunosuppressive
therapy will be treated according to the standard of care, hATG/cyclosporine, in addition to
eltrombopag. Patients with relapsed/refractory SAA or recurrent AA will be enrolled into one
of two treatment options: hATG/cyclosporine plus eltrombopag or cyclosporine plus
eltrombopag, depending on prior treatment with immunosuppressive therapy.

After initiating treatment with eltrombopag, patients will have their dose assessed and
modified as tolerated, until the targeted platelet count or maximum dose is achieved.
Pharmacokinetic assessments will be performed at time points intended to capture steady state
PK of the starting dose and highest dose achieved.

Upon completion of the Treatment and Follow-Up Periods, all patients will be offered the
opportunity to enroll in an additional 3 year Long Term Follow-Up Period.


For Cohort A:

1. Prior history of diagnosis of SAA

2. Diagnosis of relapsed/refractory SAA or recurrent AA following IST for SAA at the time
of enrollment. Patients with recurrent AA (e.g., losing their response) are exempt
from meeting the diagnostic criteria for relapsed SAA at the time of enrollment, but
must have been previously diagnosed with SAA.

3. Agree to concurrent eltrombopag treatment with appropriate, investigator-selected IST
with either hATG + CsA or CsA.

For Cohort B:

4. Diagnosis of SAA at the time of enrollment

5. Patients must not have been previously treated for SAA

6. Patients must agree to treatment with hATG + CsA concurrent with eltrombopag.

For all patients, regardless of cohort:

7. Age 1 to <18 years

8. Where appropriate, assessments to rule out congenital/inherited bone marrow failure
syndromes and other causes of immune-mediated pancytopenia, which may be treated with
transplant, must be completed prior to enrollment.

9. Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a
treatment option or has been refused by the patient. (Candidacy for HSCT will be
determined as per local practice.)

10. Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of
eltrombopag

11. Normal karyotype with FISH for chromosomes 7 and 8

12. Performance status score: Karnofsky ≥50 or Lansky ≥50 (depending on age)

13. Serum creatinine ≤2.5 × ULN

14. Total bilirubin ≤1.5 × ULN

15. Written informed consent signed by a parent or legal guardian prior to initiation of
any study specific procedure.

Exclusion Criteria:

1. Prior and/or active medical history of:

- Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry)

- Other known underlying congenital/inherited marrow failure syndromes

- Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones >50% of
PMN or RBC at time of enrollment

- Any cytogenetic abnormalities, including but not limited to chromosome 7 or
myelodysplasia, in bone marrow within 4 weeks of study enrollment

- Myelodysplastic syndrome (MDS)

- Other known or suspected underlying primary immunodeficiency

- Any malignancy

2. Active infection not responding to appropriate therapy

3. Prior eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at
least 2 months and a lack of response.

4. Any out of range lab values Creatinine >2.5 × upper limit of normal (ULN), Total
bilirubin >1.5 × ULN Aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) >2.5 × ULN
We found this trial at
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13123 E 16th Ave
Aurora, Colorado 80045
(720) 777-1234
Principal Investigator: Taizo Nakano
Phone: 720-777-6353
Children's Hospital Colorado At Children's Hospital Colorado, we see more, treat more and heal more...
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Ann Arbor, Michigan 48109
Principal Investigator: Kelly Walkovich
Phone: 734-936-1854
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Atlanta, Georgia 30342
Principal Investigator: Carolyn Bennett
Phone: 404-785-2025
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Boston, Massachusetts 02115
Principal Investigator: Akiko Shimamura
Phone: 617-355-4685
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Chicago, Illinois 60611
Principal Investigator: Alexis Thompson
Phone: 312-227-4825
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Cleveland, Ohio 44195
Principal Investigator: Rabi Hanna
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Columbus, Ohio 43205
Principal Investigator: Melissa Rose
Phone: 614-722-6885
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Durham, North Carolina 27710
Principal Investigator: Jennifer Rothman
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Gainesville, Florida 32610
Principal Investigator: Paul Castillo
Phone: 352-273-9050
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Hackensack, New Jersey 07601
Principal Investigator: Alfred Gillio
Phone: 551-996-3457
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Houston, Texas 77030
Principal Investigator: Alison Bertuch
Phone: 832-824-4825
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Indianapolis, Indiana 46202
Principal Investigator: Grzegorz Nalepa
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Little Rock, Arkansas 72202
Principal Investigator: Jason Farrar
Phone: 501-364-4181
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Madison, Wisconsin 53792
Principal Investigator: Inga Hofmann
Phone: 608-890-8070
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Philadelphia, Pennsylvania 19104
Principal Investigator: Timothy Olson
Phone: 267-426-9989
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Phoenix, Arizona 85016
Principal Investigator: Jessica Boklan
Phone: 602-933-0171
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Principal Investigator: Amy Geddis
Phone: 206-987-4329
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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