ファンコニ貧血患者に対するエルトロンボパグ

Participants with Fanconi anemia will receive daily eltrombopag. Doses will be administered as follows:

Non Asian populations

• Ages 6 to 11: 75 mg daily; may increase up to 150 mg during the extension phase.
• Ages 12 and older: 150 mg daily; may increase up to 300 mg during the extension phase.

East Asian, South East Asian populations

• Ages 6 to 11: 37.5 mg daily; may increase up to 150 mg during the extension phase.
• Ages 12 and older: 75 mg daily; may increase up to 300 mg during the extension phase.

Daily dose (first 6 months)

• Non-Asian (6-11): 75 mg
• Non-Asian (>=12): 150 mg
• East Asian, South East Asian (6-11): 37.5 mg
• East Asian, South East Asian (>=12): 75 mg

• EPAG

Defined as one or more of the following:

Peripheral Blood Response:

• Platelet count increases of at least 20,000/uL above baseline or stable platelet counts with transfusion independence for those participants that were transfusion dependent prior to treatment for a minimum of 8 consecutive weeks prior to response assessment;
• An increase in hemoglobin by > 1.5g/dL or a reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks;
• At least a 100% increase in ANC in participants with a pretreatment absolute neutrophil count (ANC) of <0.5 x 10^9/L, or an ANC increase >0.5 x 10^9/L

Bone Marrow Response:

• >= 2-fold increase in normal marrow CD34+ cells by CD34 immunohistochemistry or flow cytometry, and/or
• >= 2-fold increase in normal marrow cellularity as measured by standard stains (H&E) of bone marrow biopsy/aspirate sections.

The table reports the number of participants with at least one related adverse event overall and, for each event term, the number by maximum grade (Grade 1-2 or Grade 3 or higher). Each participant was counted once in the overall row and once per event term at the highest grade experienced; event-term categories are not mutually exclusive.

Adverse events were assessed by the investigator as possibly, probably, or definitely related to eltrombopag, and were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), and Grade 5 (death related to adverse event).

Participants with an evaluable Month 3 assessment were responders if they met at least one criterion:

1. platelet response: platelet count increased by ≥20,000/µL from baseline, or, if platelet-transfusion dependent before treatment, stable counts with transfusion independence for ≥8 consecutive weeks before assessment;
2. erythroid response: hemoglobin increased by >1.5 g/dL, or packed red blood cell transfusion units decreased by ≥50% during the 8 weeks before assessment versus the 8 weeks before treatment;
3. neutrophil response: for pretreatment absolute neutrophil count <0.5 × 10^9/L, absolute neutrophil count increased by ≥100% or by >0.5 × 10^9/L; or
4. bone marrow response: ≥2-fold increase from baseline in normal marrow CD34-positive cells by immunohistochemistry or flow cytometry and/or ≥2-fold increase in marrow cellularity by hematoxylin and eosin staining.

Within-participant change from baseline in health-related quality-of-life scores at Months 3 and 6. Age-appropriate adult, pediatric, or parent-proxy questionnaires were used, as applicable. The protocol-specified measures included:

• Patient-Reported Outcomes Measurement Information System Global Health.
• Patient-Reported Outcomes Measurement Information System Sleep Disturbance.
• Patient-Reported Outcomes Measurement Information System Applied Cognition-Abilities.
• Patient-Reported Outcomes Measurement Information System Anxiety.
• Patient-Reported Outcomes Measurement Information System Depression.
• Functional Assessment of Cancer Therapy measures addressing anemia, thrombocytopenia, and neutropenia.

Changes from baseline were summarized separately for each instrument or domain and evaluated overall and in relation to hematologic treatment response.