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hATG+CsA vs hATG+CsA+Eltrombopag for SAA (RACE)

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ClinicalTrials.gov Identifier: NCT02099747
Recruitment Status : Active, not recruiting
First Posted : March 31, 2014
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
Novartis
Pfizer
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation

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
Severe Aplastic Anemia Drug: hATG Drug: CsA Drug: Eltrombopag 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.

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Study Type : Interventional  (Clinical Trial)
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.
Study Start Date : July 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Eltrombopag

Arm Intervention/treatment
Active Comparator: hATG + CsA
Control Arm
Drug: hATG
Other Name: ATGAM

Drug: CsA
Experimental: hATG + CsA + Eltrombopag
Experimental
Drug: hATG
Other Name: ATGAM

Drug: CsA
Drug: Eltrombopag



Primary Outcome Measures :
  1. CR rate [ Time Frame: 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 [ Time Frame: 2 year ]
  2. Heamatological Response at 6, 12, 18 and 24 months [ Time Frame: 2 year ]
  3. Cumulative incidence of response [ Time Frame: 2 year ]
  4. Overall survival [ Time Frame: 2 year ]
  5. Event-free survival [ Time Frame: 2 year ]
  6. Cumulative incidence of relapse rate [ Time Frame: 2 year ]
  7. Cumulative incidences of clonal evolution [ Time Frame: 2 year ]
  8. Cumulative incidence of PNH population occurrence and clinical hemolytic PNH occurrence [ Time Frame: 2 year ]
  9. Cumulative incidence of discontinuation of immunosuppressive therapy [ Time Frame: 2 year ]
  10. Rate of CsA-independent hematological response at 24 months [ Time Frame: 2 year ]
  11. Need for transfusions and number of transfusions required from treatment [ Time Frame: 2 year ]
  12. Need for any supportive care [ Time Frame: 2 year ]
  13. 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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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02099747


Locations
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France
Hopital Jean Minjoz
Besancon, France
Hôpital Haut-Lévèque
Bordeaux, France
Hôpital Huriez
Lille, France
Centre Hospitalier Lyon-Sud
Lyon, France
St. Louis Hospital
Paris, France
Pontchaillou Hospital
Rennes, France
Hôpital Purpan
Toulouse, France
Italy
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, Italy
Istituto G. Gaslini children's Hospital
Genova, Italy
San Martino Hospital
Genova, Italy
Fondazione IRCCS ca Granda Ospedale
Milan, Italy
`Federico II` Medical School
Naples, Italy
La Sapienza University Hospital
Rome, Italy
AOU Città della Salute e della Scienza di Torino
Turin, Italy
Netherlands
AMC
Amsterdam, Netherlands
UMCG
Groningen, Netherlands
Leiden University Medical Center
Leiden, Netherlands
UMCU
Utrecht, Netherlands
Spain
Hospital Universitari Germans Trias I Pujol
Badalona, Spain
Institut Català d'Oncologia - Hospital Duran i Reynals
Barcelona, Spain
Donostia Hospital
San Sebastian, Spain
Hospital La Fe
Valencia, Spain
Switzerland
University Hospital Basel
Basel, Switzerland
University Hospital Bern
Bern, Switzerland
University Hospital Zürich
Zürich, Switzerland
United Kingdom
St. James Hospital
Leeds, United Kingdom
King's College Hospital
London, United Kingdom
St. Bartholomew's Hospital
London, United Kingdom
City Hospital
Nottingham, United Kingdom
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Novartis
Pfizer
Investigators
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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

Additional Information:
RACE  This link exits the ClinicalTrials.gov site

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Responsible Party: European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT02099747     History of Changes
Other Study ID Numbers: EBMT-RACE
2014-000363-40 ( EudraCT Number )
First Posted: March 31, 2014    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: April 2019
Keywords provided by European Group for Blood and Marrow Transplantation:
Aplastic Anaemia
Eltrombopag
HATG
ATGAM
Additional relevant MeSH terms:
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Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases