A phase II dose escalation study: use of eltrombopag in pediatric patients with severe aplastic anemia or recurrent aplastic anemia

Phase 1

• Conditions: Refractory, relapsed or treatment naïve severe aplastic anemia (SAA) or recurrent aplastic anemia (AA); MedDRA version: 20.0Level: PTClassification code 10002967Term: Aplastic anaemiaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2015-003166-91-NL
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-08
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Inclusion Criteria specific to Cohort A (patients with relapsed/refractory
SAA or recurrent AA):
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.
Inclusion Criteria specific to Cohort B (patients with previously
untreated SAA):
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.
Inclusion Criteria 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/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 x ULN
14. Total bilirubin = 1.5 x ULN
15. Written informed consent signed by a parent or legal guardian prior
to initiation of any study specific procedure.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 (such as, but not limited to, Dyskeratosis Congenita, Congenital Amegakaryocytic Thrombocytopenia, or Shwachman-Diamond Syndrome).
• 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified