Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF)

Study Overview
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Brief Summary
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The purpose of this study is to examine the effect of G-CSF on disease free survival and overall survival in aplastic anaemia patients who also receive ATG and Cyclosporin A.

Detailed Description
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Open label, randomized, controlled study of G-CSF, ATG and Cyclosporin A versus ATG and Cyclosporin A. Subjects will be evaluated for hematologic response through day 240. Subjects who do not demonstrate a partial or complete remission by day 120 will be randomized to receive either a second course of ATG or continue their current regimen. Subjects who do demonstrate a partial or complete remission will continue their current regimen through day 240 or maintenance of a complete remission for 30 days. The last day of study treatment will be day 240.

Official Title
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A RANDOMIZED CONTROLLED STUDY IN NEWLY DIAGNOSED SEVERE APLASTIC ANEMIA PATIENTS RECEIVING ANTITHYMOCYTE GLOBULIN (ATG), CYCLOSPORIN A, WITH OR WITHOUT G-CSF

Conditions
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Aplastic Anaemia

Intervention / Treatment
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* Drug: G-CSF
* Drug: Early retreatment with ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe or very severe aplastic anemia Less than 6 months from diagnosis of severe aplastic anemia by bone marrow biopsy Ethical - Before randomization is done the subject or legally acceptable representative must give written informed consent for participation in the study Exclusion Criteria: Eligibility for an HLA-matched sibling donor transplant Prior therapy with ATG Cyclosporin A <4 weeks before enrollment Treatment with G-CSF <2 weeks before enrollment Other growth factors <4 weeks before enrollment Diagnosis of Fanconi anemia, dyskeratosis congenita or congenital bone marrow failure syndrome Evidence of myelodysplastic disease Diagnosis or previous history of carcinoma (except local cervical, basal cell, squamous cells, or melanoma) Subjects who have infection, hepatic, renal cardiac, metabolic or other concurrent diseases of such severity that death is imminent Subject is pregnant (e.g. positive HCG test) or is breast feeding
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No G-CSF, No 2nd ATG<br>Patients randomised not to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response. | Drug: G-CSF<br>* Yes/no addition of G-CSF<br>Drug: Early retreatment with ATG<br>* Yes/no early retreatment with ATG<br>|
| Active Comparator: No G-CSF, yes 2nd ATG<br>Patients randomised not to receive G-CSF (alongside ATG and CSA) but they do receive early retreatment in case of no response. | Drug: G-CSF<br>* Yes/no addition of G-CSF<br>Drug: Early retreatment with ATG<br>* Yes/no early retreatment with ATG<br>|
| Active Comparator: Yes G-CSF, No 2nd ATG<br>Patients randomised to receive G-CSF (alongside ATG and CSA) and to not receive early retreatment in case of no response. | Drug: G-CSF<br>* Yes/no addition of G-CSF<br>Drug: Early retreatment with ATG<br>* Yes/no early retreatment with ATG<br>|
| Active Comparator: Yes G-CSF, Yes 2nd ATG<br>Patients randomised to receive G-CSF (alongside ATG and CSA) and to receive early retreatment in case of no response. | Drug: G-CSF<br>* Yes/no addition of G-CSF<br>Drug: Early retreatment with ATG<br>* Yes/no early retreatment with ATG<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure free survival | To evaluate the effect of G-CSF on failure free survival and mortality in study subjects also receiving ATG and Cyclosporin A & time to hematologic response (failure defined as death, non-response or requirement of further treatment). | day 240 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematological response | The proportion of subjects who achieve a hematologic response | day 240 | 
| Severe Infections | Incidence of severe infections | day 240 | 
| Benefit of addition of G-CSF | The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii) | day 240 | 
| Complete remission | Time to achieving a complete remission within 120 days | day 120 | 
| Relapse rate | The relapse rate among responders | 2year | 
| Blood count | Median blood counts among subjects who achieve transfusion independence | day 240 | 
| Severity of the disease | The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia) | day 365 | 
| Retreatment with ATG | Proportion of subjects who respond to re-treatment with ATG, | day 240 | 
| Safety | The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A | 6year |