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RACE: hATG+CsA vs hATG+CsA+Eltrombopag for SAA

Sponsor
European Society for Blood and Marrow Transplantation (Other)
Overall Status
Completed
CT.gov ID
NCT02099747
Collaborator
Novartis (Industry), Pfizer (Industry)
202
Enrollment
29
Locations
2
Arms
65.1
Actual Duration (Months)
7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
202 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Jul 1, 2015
Actual Primary Completion Date :
Dec 1, 2020
Actual Study Completion Date :
Dec 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: hATG + CsA

Control Arm

Drug: hATG
Other Names:
  • ATGAM

    • Drug: CsA
    Experimental: hATG + CsA + Eltrombopag

    Experimental

    Drug: hATG
    Other Names:
  • ATGAM

    • Drug: CsA

    Drug: Eltrombopag

    Outcome Measures

    Primary Outcome Measures

    1. CR rate [3 months]

      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

    1. Time to best heamatological response [2 year]

    2. Heamatological Response at 6, 12, 18 and 24 months [2 year]

    3. Cumulative incidence of response [2 year]

    4. Overall survival [2 year]

    5. Event-free survival [2 year]

    6. Cumulative incidence of relapse rate [2 year]

    7. Cumulative incidences of clonal evolution [2 year]

    8. Cumulative incidence of PNH population occurrence and clinical hemolytic PNH occurrence [2 year]

    9. Cumulative incidence of discontinuation of immunosuppressive therapy [2 year]

    10. Rate of CsA-independent hematological response at 24 months [2 year]

    11. Need for transfusions and number of transfusions required from treatment [2 year]

    12. Need for any supportive care [2 year]

    13. Comparison of number of SAEs between the two arms [2 year]

      To look for the safety and tolerability of the investigational treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. Male or female age > 14 years;

    2. Written informed consent

    3. Willing and able to comply with all of the requirements and visits in the protocol

    4. Understands that they can be randomised to either treatment arm

    5. Negative pregnancy test for women of child bearing age

    6. 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

    1. CMV viremia, as defined by positive PCR or pp65 test

    2. WHO performance status ≥3

    3. Pregnant or breast feeding patients

    4. Patients with hepatic, renal or cardiac failure, or any other life- threatening concurrent disease

    5. Patients with HIV infection

    6. Patients without social health care assistance

    7. Participation in another clinical trial within 1 month before the start of this trial

    8. 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

    9. subjects with known hypersensitivity to any of the component medications

    The presence of a Paroxysmal Nocturnal Hemoglobinuria clone is not an exclusion criterion.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hopital Jean Minjoz Besancon France
    2 Hôpital Haut-Lévèque Bordeaux France
    3 Hôpital Huriez Lille France
    4 Centre Hospitalier Lyon-Sud Lyon France
    5 St. Louis Hospital Paris France
    6 Pontchaillou Hospital Rennes France
    7 Hôpital Purpan Toulouse France
    8 Azienda Ospedaliera Papa Giovanni XXIII Bergamo Italy
    9 Istituto G. Gaslini children's Hospital Genova Italy
    10 San Martino Hospital Genova Italy
    11 Fondazione IRCCS ca Granda Ospedale Milan Italy
    12 'Federico II' Medical School Naples Italy
    13 La Sapienza University Hospital Rome Italy
    14 AOU Città della Salute e della Scienza di Torino Turin Italy
    15 AMC Amsterdam Netherlands
    16 UMCG Groningen Netherlands
    17 Leiden University Medical Center Leiden Netherlands
    18 UMCU Utrecht Netherlands
    19 Hospital Universitari Germans Trias I Pujol Badalona Spain
    20 Institut Català d'Oncologia - Hospital Duran i Reynals Barcelona Spain
    21 Donostia Hospital San Sebastian Spain
    22 Hospital La Fe Valencia Spain
    23 University Hospital Basel Basel Switzerland
    24 University Hospital Bern Bern Switzerland
    25 University Hospital Zürich Zürich Switzerland
    26 St. James Hospital Leeds United Kingdom
    27 King's College Hospital London United Kingdom
    28 St. Bartholomew's Hospital London United Kingdom
    29 City Hospital Nottingham United Kingdom

    Sponsors and Collaborators

    • European Society for Blood and Marrow Transplantation
    • Novartis
    • Pfizer

    Investigators

    • Principal Investigator: Antonio Risitano, MD, PhD, Federico II Medical School, Haematology Division, Napels
    • Principal Investigator: Regis Peffault de Latour, MD, PhD, St. Louis Hospital, Haematology Division, Paris

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    European Society for Blood and Marrow Transplantation
    ClinicalTrials.gov Identifier:
    NCT02099747
    Other Study ID Numbers:
    • EBMT-RACE
    • 2014-000363-40
    First Posted:
    Mar 31, 2014
    Last Update Posted:
    Dec 22, 2020
    Last Verified:
    Dec 1, 2020
    Keywords provided by European Society for Blood and Marrow Transplantation
    Aplastic Anaemia
    Eltrombopag
    HATG
    ATGAM
    Additional relevant MeSH terms:
    Anemia
    Anemia, Aplastic

    Study Results

    No Results Posted as of Dec 22, 2020