Brief Title
hATG+CsA vs hATG+CsA+Eltrombopag for SAA
Official Title
A Prospective Randomized Multicenter Study Comparing Horse Antithymocyte Globuline (hATG) + Cyclosporine A (CsA) With or Without Eltrombopag as Front-line Therapy for Severe Aplastic Anemia Patients.
Brief Summary
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.
Detailed Description
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% (investigational arm) in 3 month complete response rate (two-sided binomial test); alpha-error 0.05; power 0.8.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
CR rate
Secondary Outcome
Time to best heamatological response
Condition
Severe Aplastic Anemia
Intervention
hATG
Study Arms / Comparison Groups
hATG + CsA
Description: Control Arm
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
202
Start Date
July 2015
Completion Date
December 2020
Primary Completion Date
December 2020
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.
Gender
All
Ages
15 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Antonio Risitano, MD, PhD, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT02099747
Organization ID
EBMT-RACE
Secondary IDs
2014-000363-40
Responsible Party
Sponsor
Study Sponsor
European Society for Blood and Marrow Transplantation
Collaborators
Novartis
Study Sponsor
Antonio Risitano, MD, PhD, Principal Investigator, Federico II Medical School, Haematology Division, Napels
Verification Date
December 2020