hATG+CsA vs hATG+CsA+Eltrombopag for SAA

NCT ID: NCT02099747

Last Updated: 2020-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2020-12-31

Brief Summary

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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

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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.

Conditions

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Severe Aplastic Anemia

Keywords

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Aplastic Anaemia Eltrombopag HATG ATGAM

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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hATG + CsA

Control Arm

Group Type ACTIVE_COMPARATOR

hATG

Intervention Type DRUG

CsA

Intervention Type DRUG

hATG + CsA + Eltrombopag

Experimental

Group Type EXPERIMENTAL

hATG

Intervention Type DRUG

CsA

Intervention Type DRUG

Eltrombopag

Intervention Type DRUG

Interventions

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hATG

Intervention Type DRUG

CsA

Intervention Type DRUG

Eltrombopag

Intervention Type DRUG

Other Intervention Names

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ATGAM

Eligibility Criteria

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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.
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

European Society for Blood and Marrow Transplantation

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Antonio Risitano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Federico II Medical School, Haematology Division, Napels

Regis Peffault de Latour, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Louis Hospital, Haematology Division, Paris

Locations

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Hopital Jean Minjoz

Besançon, , France

Site Status

Hôpital Haut-Lévèque

Bordeaux, , France

Site Status

Hôpital Huriez

Lille, , France

Site Status

Centre Hospitalier Lyon-Sud

Lyon, , France

Site Status

St. Louis Hospital

Paris, , France

Site Status

Pontchaillou Hospital

Rennes, , France

Site Status

Hôpital Purpan

Toulouse, , France

Site Status

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Site Status

Istituto G. Gaslini children's Hospital

Genova, , Italy

Site Status

San Martino Hospital

Genova, , Italy

Site Status

Fondazione IRCCS ca Granda Ospedale

Milan, , Italy

Site Status

'Federico II' Medical School

Naples, , Italy

Site Status

La Sapienza University Hospital

Rome, , Italy

Site Status

AOU Città della Salute e della Scienza di Torino

Turin, , Italy

Site Status

AMC

Amsterdam, , Netherlands

Site Status

UMCG

Groningen, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

UMCU

Utrecht, , Netherlands

Site Status

Hospital Universitari Germans Trias I Pujol

Badalona, , Spain

Site Status

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Donostia Hospital

Donostia / San Sebastian, , Spain

Site Status

Hospital La Fe

Valencia, , Spain

Site Status

University Hospital Basel

Basel, , Switzerland

Site Status

University Hospital Bern

Bern, , Switzerland

Site Status

University Hospital Zürich

Zurich, , Switzerland

Site Status

St. James Hospital

Leeds, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

St. Bartholomew's Hospital

London, , United Kingdom

Site Status

City Hospital

Nottingham, , United Kingdom

Site Status

Countries

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Germany France Italy Netherlands Spain Switzerland United Kingdom

References

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de Latour RP, Kulasekararaj A, Iacobelli S, Griffin M, Halkes CJ, Dufour C, Risitano AM. Plain language summary of RACE study results: addition of eltrombopag to standard treatment of severe aplastic anemia. Immunotherapy. 2024 Feb;16(3):135-142. doi: 10.2217/imt-2023-0200. Epub 2023 Dec 13.

Reference Type DERIVED
PMID: 38088156 (View on PubMed)

Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, Halkes CJM, Recher C, Barraco F, Forcade E, Vallejo JC, Drexler B, Mear JB, Smith AE, Angelucci E, Raymakers RAP, de Groot MR, Daguindau E, Nur E, Barcellini W, Russell NH, Terriou L, Iori AP, La Rocca U, Sureda A, Sanchez-Ortega I, Xicoy B, Jarque I, Cavenagh J, Sicre de Fontbrune F, Marotta S, Munir T, Tjon JML, Tavitian S, Praire A, Clement L, Rabian F, Marano L, Hill A, Palmisani E, Muus P, Cacace F, Frieri C, van Lint MT, Passweg JR, Marsh JCW, Socie G, Mufti GJ, Dufour C, Risitano AM; Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation. Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med. 2022 Jan 6;386(1):11-23. doi: 10.1056/NEJMoa2109965.

Reference Type DERIVED
PMID: 34986284 (View on PubMed)

Other Identifiers

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2014-000363-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EBMT-RACE

Identifier Type: -

Identifier Source: org_study_id