Aplastic Anaemia
Conditions
Brief summary
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
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.
Interventions
DRUGG-CSF
Yes/no addition of G-CSF
DRUGEarly retreatment with ATG
Yes/no early retreatment with ATG
Sponsors
European Society for Blood and Marrow Transplantation
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure free survival | day 240 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Haematological response | day 240 | The proportion of subjects who achieve a hematologic response |
| Severe Infections | day 240 | Incidence of severe infections |
| Benefit of addition of G-CSF | day 240 | The benefit due to the addition of G-CSF on death rate (i), days of hospitalization (ii), and duration of antibiotic treatment (iii) |
| Complete remission | day 120 | Time to achieving a complete remission within 120 days |
| Relapse rate | 2year | The relapse rate among responders |
| Blood count | day 240 | Median blood counts among subjects who achieve transfusion independence |
| Severity of the disease | day 365 | The proportion of subjects who have a change in severity of disease (e.g. improvement from very severe to severe aplastic anemia) |
| Retreatment with ATG | day 240 | Proportion of subjects who respond to re-treatment with ATG, |
| Safety | 6year | The safety of G-CSF in subjects treated with G-CSF, ATG and Cyclosporin A, compared to subjects who receive ATG and Cyclosporin A |
Countries
Czechia, France, Germany, Greece, Italy, Netherlands, Sweden, Switzerland, United Kingdom
Contacts
PRINCIPAL_INVESTIGATORAndré Tichelli, Prof. MD.
University Hospital, Basel, Switzerland
Outcome results
None listed