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Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia or in Relapse After Immunosuppression

RecruitingPhase 2Ages 3 Years - 35 YearsAllAssistance Publique - Hôpitaux de Paris
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In plain words

What the trial is, and whether it could suit you

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

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📋 Eligibility rules (as published)
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
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What it tests

  • Allogenic transplantation
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Where

35 sites
CHU Amiens
Amiens, France
CHU Angers
Angers, France
CHU Besancon
Besançon, France
CHU Bordeaux
Bordeaux, France
Hôpital du Haut-Lévêque
Bordeaux, France
CHU Caen
Caen, France
Hopital Percy
Clamart, France
CHU Clermont
Clermont-Ferrand, France

…and 27 more on ClinicalTrials.gov.

🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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