hATG+CsA vs hATG+CsA+Eltrombopag for SAA

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 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

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