Informations générales (source: ClinicalTrials.gov)
Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia or in Relapse After Immunosuppression: a Nationwide Phase II Study
Interventional
Phase 2
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
janvier 2022
janvier 2027
14 septembre 2025
Outcomes for patients with severe aplastic anemia (SAA) who are refractory to first-line
immunosuppressive therapy (IST) and who lack a matched unrelated donor (MUD) remain poor.
Recently, the use of eltrombopag (ELT) has shown blood count improvements in 40% of these
patients. However, most refractory patients do not respond to ELT or other second-line
treatment and are therefore exposed to life-threatening infections, and bleeding. During
the past 2 decades, there has been a significant decrease in infection-related mortality
in patients with SAA unresponsive to initial IST but clonal evolution including
paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), and acute
myeloid leukemia (AML) still occur in the long-term with a grim prognosis. Overall, the
overall survival of such patients with acquired refractory SAA to ELT is about 60-70% at
2 years.
Hematopoietic stem cell transplantation (HSCT) using alternative donor sources (i.e.,
mismatched unrelated donors, cord blood (CBT), and haplo-identical family donors) may be
curative in patients with refractory SAA, despite carrying much higher rates of
complications than in transplantations from matched related or unrelated donors.
Recently, our group showed that CBT is a valuable curative option for young adults with
refractory SAA. However, not all patients have available CB and CBT treatment related
mortality is high in adult patients. Haploidentical (haplo) related donor Stem Cell
Transplantation (haplo-SCT) have improved dramatically outcomes using T-cell replete
grafts with administration of post-transplantation cyclophosphamide (PTCy). Preliminary
results in a little number of patients with refractory SAA at Kings college (London, UK)
and John Hopkins (Baltimore, USA) seem promising. The investigators retrospectively
analyzed data from 36 patients (median age 42 years) transplanted between 2010 and 2017
in Europe on behalf of the SAA working party of the European Blood and Marrow
Transplantation group. The 1-year overall survival was about 80% suggesting that this
approach might be a valid option in this particular poor clinical situation.
The main objective of this study is to demonstrate a benefit in term of the 2-year
overall survival rate from 60% (historical rates in patients with acquired refractory
idiopathic aplastic anemia) up to 80% using haplo-SCT with PTCy.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HIA PERCY | PEFFAULT DE LA TOUR Regis | 13/12/2025 07:24:55 | Contacter | ||
| AP-HP Assistance publique - Hôpitaux de Paris | 13/12/2025 07:24:55 | Contacter | |||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | |||||
| AP-HP - Hôpital La Pitié-Salpêtrière | |||||
| AP-HP - Hôpital Lariboisiere-Fernand Widal | |||||
| AP-HP - Hôpital Necker-Enfants Malades | |||||
| AP-HP - Hôpital Robert Debré | |||||
| AP-HP - Hôpital Saint Antoine | |||||
| AP-HP - Hôpital Saint Louis | |||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHRU Strasbourg - Strasbourg - France | Bruno Lioure | Contact (sur clinicalTrials) | |||
| CHU Amiens - Amiens - France | Amandine Charbonnier | Contact (sur clinicalTrials) | |||
| CHU Angers - Angers - France | Sylvie Francois | Contact (sur clinicalTrials) | |||
| CHU Besancon - Besançon - France | Ana Berceanu | Contact (sur clinicalTrials) | |||
| CHU Bordeaux - Bordeaux - France | Charlotte Jubert | Contact (sur clinicalTrials) | |||
| CHU Caen - Caen - France | Sylvain Chantepie | Contact (sur clinicalTrials) | |||
| CHU Clermont - Clermont-Ferrand - France | Olivier Bay Jacques | Contact (sur clinicalTrials) | |||
| CHU Grenoble - Grenoble - France | Claude-Eric Bulabois | Contact (sur clinicalTrials) | |||
| CHU Lille - Lille - France | Bénédicte Bruno | Contact (sur clinicalTrials) | |||
| CHU Limoges - Limoges - France | Pascal Turlure | Contact (sur clinicalTrials) | |||
| CHU Lyon Sud - Lyon - France | Fiorenza Barroco | Contact (sur clinicalTrials) | |||
| CHU Montpellier - Montpellier - France | Anne Sirvent | Contact (sur clinicalTrials) | |||
| CHU Nancy - Nancy - France | Maud d'Aveni | Contact (sur clinicalTrials) | |||
| CHU Nantes - Nantes - France | Fanny Rialland | Contact (sur clinicalTrials) | |||
| CHU Nice - Nice - France | Michael Loschi | Contact (sur clinicalTrials) | |||
| CHU Poitiers - Poitiers - France | Natacha Maillard | Contact (sur clinicalTrials) | |||
| CHU Rennes - Rennes - France | Virginie Gandemer | Contact (sur clinicalTrials) | |||
| CHU Toulouse - Toulouse - France | Anne Huynh | Contact (sur clinicalTrials) | |||
| CHU-Estaing_Clermont Ferrand - Clermont-Ferrand - France | Justyna Kanold | Contact (sur clinicalTrials) | |||
| Crlcc Henri Becquerel Rouen - Rouen - France | Nathalie Contentin | Contact (sur clinicalTrials) | |||
| Henri Mondor - Créteil - France | Sébastien Maury | Contact (sur clinicalTrials) | |||
| Hôpital du Haut-Lévêque - Bordeaux - France | Edouard Forcade | Contact (sur clinicalTrials) | |||
| Hopital La Timone - Marseille - France | Arthur Sterin | Contact (sur clinicalTrials) | |||
| Hopital Percy - Clamart - France | Johanna Konopacki | Contact (sur clinicalTrials) | |||
| Hopital Robert Debré - Paris - France | Jean-Hugues Dalle | Contact (sur clinicalTrials) | |||
| Hôpital Saint Louis - Paris - France | Régis Peffault de Latour | Contact (sur clinicalTrials) | |||
| ICLN_Saint Priest En Jarez - Saint-Priest-en-Jarez - France | Jérôme Cornillon | Contact (sur clinicalTrials) | |||
| IHOP, CHU Lyon - Lyon - France | Cécile Renard | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Aged from 3 to 35 years old
- Suffering from refractory acquired idiopathic aplastic anemia (at least one course
of immunosuppression with anti-thymocyte globulin)
- Absence of geno-identical donor or 10/10 matched donor
- With identification of a haploidentical donor (brother, sister, parents, adult
children or cousin)
- Absence of donor specific antibody detected in the patient with a MFI ≥ 1500
(antibodies directed towards the distinct haplotype between donor and recipient)
- With usual criteria for HSCT :
- ECOG(Eastern Cooperative Oncology Group) ≤ 2
- No severe and uncontrolled infection
- Cardiac function compatible with high dose of cyclophosphamide
- Adequate organ function: ASAT(aspartate transaminase) and ALAT (alanine
aminotransferase) ≤ 2.5 N (the norm), total bilirubin ≤ 2N, creatinine < 150 μmol/L
- With health insurance coverage
- Contraception methods must be prescribed during all the duration of the research.
Women and men of childbearing age must use contraceptive methods within 12 months
and 6 months after the last dose of cyclophosphamide, respectively.
- Having signed a written informed consent (2 parents for patients aged less than 18)
Exclusion Criteria :
- With morphologic evidence of clonal evolution (patients with isolated bone marrow
cytogenetic abnormalities are also eligible excepted chromosome 7 abnormalities and
complex karyotype)
- With uncontrolled infection
- With seropositivity for HIV or HTLV-1 (Human T cell Leukemia) or active hepatitis B
or C defined by a positive PCR (polymerase chain reaction) HBV (hepatitis B virus)
or HCV (hepatitis C virus) and associated hepatic cytolysis
- Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ"
carcinoma of the cervix)
- Pregnant (βHCG positive) or breast-feeding.
- Who received live attenuated vaccine within 2 months before transplantation and
during the research
- Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current
manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular
ejection fraction <50%
- With heart failure according to NYHA (New York Heart Association) (II or more)
- Preexisting acute hemorrhagic cystitis
- Renal failure with creatinine clearance <30ml / min
- With urinary tract obstruction
- Who receive the following treatments Phenytoin, Pentostatin, inhibitor of adenoside)
- Who have any debilitating medical or psychiatric illness, which preclude
understanding the inform consent as well as optimal treatment and follow-up
- Under tutorship or curatorship
- Aged from 3 to 35 years old
- Suffering from refractory acquired idiopathic aplastic anemia (at least one course
of immunosuppression with anti-thymocyte globulin)
- Absence of geno-identical donor or 10/10 matched donor
- With identification of a haploidentical donor (brother, sister, parents, adult
children or cousin)
- Absence of donor specific antibody detected in the patient with a MFI ≥ 1500
(antibodies directed towards the distinct haplotype between donor and recipient)
- With usual criteria for HSCT :
- ECOG(Eastern Cooperative Oncology Group) ≤ 2
- No severe and uncontrolled infection
- Cardiac function compatible with high dose of cyclophosphamide
- Adequate organ function: ASAT(aspartate transaminase) and ALAT (alanine
aminotransferase) ≤ 2.5 N (the norm), total bilirubin ≤ 2N, creatinine < 150 μmol/L
- With health insurance coverage
- Contraception methods must be prescribed during all the duration of the research.
Women and men of childbearing age must use contraceptive methods within 12 months
and 6 months after the last dose of cyclophosphamide, respectively.
- Having signed a written informed consent (2 parents for patients aged less than 18)
Exclusion Criteria :
- With morphologic evidence of clonal evolution (patients with isolated bone marrow
cytogenetic abnormalities are also eligible excepted chromosome 7 abnormalities and
complex karyotype)
- With uncontrolled infection
- With seropositivity for HIV or HTLV-1 (Human T cell Leukemia) or active hepatitis B
or C defined by a positive PCR (polymerase chain reaction) HBV (hepatitis B virus)
or HCV (hepatitis C virus) and associated hepatic cytolysis
- Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ"
carcinoma of the cervix)
- Pregnant (βHCG positive) or breast-feeding.
- Who received live attenuated vaccine within 2 months before transplantation and
during the research
- Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current
manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular
ejection fraction <50%
- With heart failure according to NYHA (New York Heart Association) (II or more)
- Preexisting acute hemorrhagic cystitis
- Renal failure with creatinine clearance <30ml / min
- With urinary tract obstruction
- Who receive the following treatments Phenytoin, Pentostatin, inhibitor of adenoside)
- Who have any debilitating medical or psychiatric illness, which preclude
understanding the inform consent as well as optimal treatment and follow-up
- Under tutorship or curatorship