RACE 2: a Long Term Follow-up of Patients Participating in the RACE Trial

Study Overview
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Brief Summary
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After exiting the RACE trial (NCT02099747) patients will be invited to participate in this long term follow-up study

Detailed Description
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Patients will be followed up annually, according to standard of care. All diagnostic and therapeutic intervention will be performed according to standard of care, at discretion of the treating physician. In particular, during the study no extra Peripheral blood or Bone Marrow sampling will be performed, in addition to routine sampling for morphology and karyotype surveillance. Molecular analysis by Next Generation Sequencing (NGS) will also be collected if the centre is doing this on a routine basis. No Investigational Medicinal Product (IMP) or Non-Investigational Medicinal Product (NIMP) will be given to the patients.

Official Title
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Long-term Follow-up of Patients Participating in RACE: the Prospective Randomized Multicenter Study Comparing Horse Antithymocyte Globuline (hATG) + Cyclosporine A (CsA) With or Without Eltrombopag as Front-line Therapy for Severe Aplastic Anemia Patients

Conditions
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Severe Aplastic Anemia

Intervention / Treatment
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* Drug: ATGAM plus CsA with or without Eltrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject participated in the RACE trial (NCT02099747, EudraCT number: 2014-000363-40) during which patient received ATGAM, Cyclosporine A with or without Eltrombopag. Subject has provided informed consent to participate in long-term data collection Exclusion Criteria: None

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RACE 1 patients<br>After exiting the RACE trial (NCT02099747) patient will be invited to participate in this study | Drug: ATGAM plus CsA with or without Eltrombopag<br>* Standard treatment with or without Eltrombopag<br>* Other names: hATG+CsA +/- Revolade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure Free Survival | Failure Free Survival, where treatment failure is defined as one or more of the following: death, relapse, malignant clonal evolution, need for further (e.g. transplant) | 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate: number of patients who reach a hematological response | Response Rate | 15 years | 
| Overall Survival | Overall Survival | 15 years | 
| Cumulative incidence of relapse after response | Cumulative incidence of relapse after initial hematological response (complete or partial) | 15 years | 
| Cumulative incidence of clonal evolution | Cumulative incidence of clonal evolution: Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) or karyotypic abnormalities qualifying for the diagnosis of MDS (see World Health Organization (WHO) 2016) | 15 years | 
| Cumulative incidence of clinical Paroxysmal nocturnal hemoglobinuria (PNH) | Cumulative incidence of clinical PNH (hemolysis and/or thromboembolism), and of need of anti-complement treatment | 15 years | 
| Cumulative incidence of Solid Tumors | Cumulative incidence of solid tumours | 15 years | 
| Number of patients who need a Human Stem Cell Transplantation (HSCT) | Need for HSCT | 15 years | 
| Number of patients who need additional IST | Need for additional intensive Imune Suppressive Therapy (IST) (e.g. ATG, alemtuzumab or cyclophosphamide-based, or any other lymphocyte-depleting agent) | 15 years | 
| Number of patients who need Maintenance IST (e.g. CsA beyond 2 years) | Need for maintenance intensive IST (e.g. CsA beyond 2 years) | 15 years | 
| Number of patients who need additional Eltrombopag (EPAG) | Need for additional EPAG | 15 years | 
| Number of patients who need any other approved Aplastic Anemia (AA) treatment | Need for any other approved Aplastic Anemia (AA) treatment | 15 years | 
| Monitoring of Clonal Hematopoiesis of Indetermined Potential (CHIP) | As tracked by somatic mutations in genes associated with myeloid disorders | 15 years |