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ClinicalTrials.gov Identifier: NCT02099747
Recruitment Status :
Active, not recruiting
First Posted : March 31, 2014
Last Update Posted : August 12, 2019
European Group for Blood and Marrow Transplantation
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation
The null hypothesis of no difference in CR% at 3 months between the arms will be tested against the alternative of a difference in CR% at an alpha level of .05 by assessing the odds ratio for arm yielded by this model.
Condition or disease
Severe Aplastic Anemia
Drug: hATGDrug: CsADrug: Eltrombopag
This is a superiority trial aiming to increase the 3 month complete response rate. The sample size is calculated on the hypothesis that the experimental treatment will increase the 3 months response rate up to 21% (by 3 folds, based on the 7% reported in Scheinberg et al ). Under these assumptions, the sample size to reject the null hypothesis is n=96 patients for each treatment arm, increased by 4% for possibly not evaluable patients (total number of 200 patients, 100 each treatment arm). Statistical design for sample size calculation: increase from 7% (control arm) to 21% (investigational arm) in 3 month complete response rate (two-sided binomial test); alpha-error 0.05; power 0.8.
The primary objective of this trial is to investigate whether Eltrombopag added to standard immunosuppressive treatment increases the rate of early (at three months) complete response in untreated AA patient.
Secondary Outcome Measures :
Time to best heamatological response [ Time Frame: 2 year ]
Heamatological Response at 6, 12, 18 and 24 months [ Time Frame: 2 year ]
Cumulative incidence of response [ Time Frame: 2 year ]
Overall survival [ Time Frame: 2 year ]
Event-free survival [ Time Frame: 2 year ]
Cumulative incidence of relapse rate [ Time Frame: 2 year ]
Cumulative incidences of clonal evolution [ Time Frame: 2 year ]
Cumulative incidence of PNH population occurrence and clinical hemolytic PNH occurrence [ Time Frame: 2 year ]
Cumulative incidence of discontinuation of immunosuppressive therapy [ Time Frame: 2 year ]
Rate of CsA-independent hematological response at 24 months [ Time Frame: 2 year ]
Need for transfusions and number of transfusions required from treatment [ Time Frame: 2 year ]
Need for any supportive care [ Time Frame: 2 year ]
Comparison of number of SAEs between the two arms [ Time Frame: 2 year ]
To look for the safety and tolerability of the investigational treatment
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Layout table for eligibility information
Ages Eligible for Study:
15 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Diagnosis of severe or very severe aplastic anemia, defined by :
At least two of the following:
Absolute neutrophil counts <0.5 x 109/L (severe) or <0.2 x 109/L (very severe)
Platelet counts <20 x 109/L
Reticulocyte counts <60 x 109/L
Hypocellular bone marrow (<30% cellularity), without evidences of fibrosis or malignant cells
Male or female age > 14 years;
Written informed consent
Willing and able to comply with all of the requirements and visits in the protocol
Understands that they can be randomised to either treatment arm
Negative pregnancy test for women of child bearing age
Written acceptance to use contraception (hormonal or barrier method of birth control; abstinence) for the entire duration of study participation.
Prior immunosuppressive therapy with ATG (horse of rabbit) or any other lymphocyte depleting agent (i.e., alemtuzumab)
Eligibility to a sibling allogeneic stem cell transplantation
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.
History or clinical suspect of constitutional aplastic anemia (i.e. Fanconi Anemia with positive DEB/MMC test or Dyskeratosis Congenita)
History of malignant tumors with active disease within 5 years from enrollment, and/or previous chemo-radiotherapy
Previous history of stem cell transplantation
Treatment with cyclosporin A unless
<4 weeks of cyclosporin A treatment before enrolement and
wash out period of 2 weeks before enrollment
CMV viremia, as defined by positive PCR or pp65 test
WHO performance status ≥3
Pregnant or breast feeding patients
Patients with hepatic, renal or cardiac failure, or any other life- threatening concurrent disease
Patients with HIV infection
Patients without social health care assistance
Participation in another clinical trial within 1 month before the start of this trial
Patients and/or female partners of male patients not using highly effective method of birth control i.e. intrauterine device (IUD), hormonal (oral pill, injection, implants), tubal ligation or partner's vasectomy
subjects with known hypersensitivity to any of the component medications
The presence of a Paroxysmal Nocturnal Hemoglobinuria clone is not an exclusion criterion.