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Trial record 1 of 1 for:    02099747
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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

Tracking Information
First Submitted Date  ICMJE March 6, 2014
First Posted Date  ICMJE March 31, 2014
Last Update Posted Date August 12, 2019
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
  • Time to best heamatological response [ Time Frame: 2 year ]
  • Heamatological Response at 6, 12, 18 and 24 months [ Time Frame: 2 year ]
  • Cumulative incidence of response [ Time Frame: 2 year ]
  • Overall survival [ Time Frame: 2 year ]
  • Event-free survival [ Time Frame: 2 year ]
  • Cumulative incidence of relapse rate [ Time Frame: 2 year ]
  • Cumulative incidences of clonal evolution [ Time Frame: 2 year ]
  • Cumulative incidence of PNH population occurrence and clinical hemolytic PNH occurrence [ Time Frame: 2 year ]
  • Cumulative incidence of discontinuation of immunosuppressive therapy [ Time Frame: 2 year ]
  • Rate of CsA-independent hematological response at 24 months [ Time Frame: 2 year ]
  • Need for transfusions and number of transfusions required from treatment [ Time Frame: 2 year ]
  • Need for any supportive care [ Time Frame: 2 year ]
  • Comparison of number of SAEs between the two arms [ Time Frame: 2 year ]
    To look for the safety and tolerability of the investigational treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE hATG+CsA vs hATG+CsA+Eltrombopag for SAA
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Severe Aplastic Anemia
Intervention  ICMJE
  • Drug: hATG
    Other Name: ATGAM
  • Drug: CsA
  • Drug: Eltrombopag
Study Arms  ICMJE
  • Active Comparator: hATG + CsA
    Control Arm
    Interventions:
    • Drug: hATG
    • Drug: CsA
  • Experimental: hATG + CsA + Eltrombopag
    Experimental
    Interventions:
    • Drug: hATG
    • Drug: CsA
    • Drug: Eltrombopag
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 8, 2019)
202
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Italy,   Netherlands,   Spain,   Switzerland,   United Kingdom
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT02099747
Other Study ID Numbers  ICMJE EBMT-RACE
2014-000363-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Group for Blood and Marrow Transplantation
Study Sponsor  ICMJE European Group for Blood and Marrow Transplantation
Collaborators  ICMJE
  • Novartis
  • Pfizer
Investigators  ICMJE
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
PRS Account European Group for Blood and Marrow Transplantation
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP