panmyelopathy
Conditions
Interventions
Two treatment arms, A and B, where subjects randomisized to arm A will receive
the standard treatment for SAA (hATG+CsA) whereas subjects randomized to arm B
will receive the experimental treatment
Eltrombopag
horse antithymocyte globuline (hATG)
Immunosuppression Therapy (IST)
Severe Aplastic Anemia (SAA)
Sponsors
European society for Blood and Marrow Transplantation
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1.Diagnosis of severe or very severe aplastic anemia, defined by ;* At least two of the following:;* Absolute neutrophil counts <0.5 x 10(9)/L (severe) or ;<0.2 x 10(9)/L (very severe);* Platelet counts <20 x 10(9)/L;* Reticulocyte counts <60 x 10(9)/L;* Hypocellular bone marrow (<30% cellularity), without evidences of fibrosis or malignant cells;2.Age * 15 years;;3.Written informed consent;4. Willing and able to comply with all of the requirements and visits in the protocol;5. Understands that they can be randomised to either treatment arm;6. Negative pregnancy test for women of child bearing age;7. Written acceptance to use contraception (hormonal or barrier method of birth control; abstinence) for the entire duration of study participation.
Exclusion criteria
Exclusion criteria: 1.Prior immunosuppressive therapy with ATG (horse of rabbit) or any other lymphocyte depleting agent (i.e., alemtuzumab);2.Eligibility to a sibling allogeneic stem cell transplantation ;3.Evidence of a myelodysplastic syndrome, defined by the presence of myelodysplastic features, excess of blasts or karyotypic abnormalities typical of MDS (according to revised WHO 2008 ;criteria) , as well as other primitive marrow disease. Patients with diagnosis of AA with cytogenetic abnormalities which are recurrent in MDS (according to revised WHO 2008 criteria) should be included in this category, and are not eligible for the study; patients with del(20q), +8 and *Y are not included in this category, and thus are eligible for this study. The list of karyotypic abnormalities which qualifies for the diagnosis of MDS are listed in the Appendix 1.;4.History or clinical suspect of constitutional aplastic anemia (i.e. Fanconi Anemia with positive DEB/MMC test or Dyskeratosis Congenita) ;5.History of malignant tumors with active disease within 5 years from enrollment and/or previous chemo-rediotherapy;6.Previous history of stem cell transplantation;7.Treatment with cyclosporin A;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of Complete response (defined as Hb >10 g/dL, ANC > 1,000/*L and Plt >100,000 *L) at 3 months since start of treatment in untreated severe AA patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to first hematological response (complete or partial) described by a cumulative incidence curve (see paragraph 9.6) 2. Time to best hematological response, described by a cumulative incidence curve (see paragraph 9.6) 3. Time to complete response (see paragraph 9.6) 4. Rates of hematological response (overall, complete, partial) at 6, 12, 18 and 24 months 5. Overall survival (OS) probability; OS is defined as time from treatment starting (day 1) to death, or last follow-up for patients alive 6. Event-free survival (EFS) probability; EFS is defined as time from treatment starting to either relapse, death, treatment failure or clonal evolution (whichever occurs first), or last follow-up for patients alive in response 7. Cumulative incidence of relapse, from first hematological response (complete or partial) (see paragraph 9.6) 8. Cumulative incidence of clonal evolution (as defined below, see 9.5): AML, MDS or karyotypic abnormalities (see paragraph 9.6) 9. Cumulative incidence of PNH population occurrence and clinical hemolytic PNH occurrence (see paragraph 9.6) 10. Cumulative incidence of discontinuation of immunosuppressive therapy 11. Rate of CsA-independent hematological response at 24 months 12. Need for transfusions (packed red cell units and platelet units) and number of transfusions required from treatment. 13. Need for any supportive care, including hospitalization 14. Quality of life (as assessed by the validated EORTC QLQ-C30 questionnaire)(changes over time and differences between treatment arms) 15. Safety and tolerability of the investigational treatment, including SAE | — |
Countries
France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom
Outcome results
None listed