hATG+CsA vs hATG+CsA+Eltrombopag for SAA

Launched by EUROPEAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION · Mar 26, 2014

Keywords

ClinConnect Summary

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 \[17\]). 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% (investiga...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• 1. Diagnosis of severe or very severe aplastic anemia, defined by \[29\]:
• * 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
• • 2. Male or female age \> 14 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:
• • 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) \[30\],, 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) \[30\] 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.
• • 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-radiotherapy
• • 6. Previous history of stem cell transplantation
• • 7. Treatment with cyclosporin A unless
• • \<4 weeks of cyclosporin A treatment before enrolement and
• • wash out period of 2 weeks before enrollment
• • 8. CMV viremia, as defined by positive PCR or pp65 test
• • 9. WHO performance status ≥3
• • 10. Pregnant or breast feeding patients
• • 11. Patients with hepatic, renal or cardiac failure, or any other life- threatening concurrent disease
• • 12. Patients with HIV infection
• • 13. Patients without social health care assistance
• • 14. Participation in another clinical trial within 1 month before the start of this trial
• • 15. 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
• • 16. subjects with known hypersensitivity to any of the component medications
• • The presence of a Paroxysmal Nocturnal Hemoglobinuria clone is not an exclusion criterion.