Indication of HSCT in Patients With Refractory/Relapse AA After First-line Standard Immunosuppressive Therapy Aged More Than 40 Years (APARR)

Assistance Publique - Hôpitaux de Paris

Status and phase

Not yet enrolling

Phase 2

Conditions

Aplastic Anemia

Treatments

Biological: Allogeneic hematopoietic stem cell transplantation Stem cell source only Bone Marrow

Study type

Interventional

Funder types

Other

Identifiers

NCT06646497

APHP230832

Details and patient eligibility

About

Outcomes for adult patients with Severe Aplastic Anemia (SAA) aged more than 40 years who are refractory or in relapse after first-line IST remain poor. Hematopoietic stem cell transplantation (HSCT) is the unic valid therapeutic option but results have always been disappointing in patients aged 40 years or older. The first cause of death after HSCT in those refractory/relapse SAA patients is still graft versus host disease (GvHD). Recently, new strategies to prevent GvHD, including T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy), have revolutionized the field, notably in haplo-identical donor setting. Using marrow as source of stem cells and a PTCy strategy not only in haplo-identical donor setting but also in case of an available matched sibling or unrelated donor might prevent drastically GvHD and eventually be practice changing. Evaluating this new strategy is the main objectives of "APARR".

Enrollment

52 estimated patients

Sex

All

Ages

40 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Aged from 40 to 60 years old
Suffering from acquired refractory severe idiopathic aplastic anemia after at least 6 months treatment with anti-thymocyte globulin, cyclosporine with Eltrombopag or in relapse
Allograft validated in the National Multidisciplinary expertise meetings of the French reference centre for aplastic anemia
With an available geno-identical donor or 10/10 matched donor or haploidentical donor
With the absence of donor specific antibody detected in the patient with a MFI < 1500 (antibodies to the distinct haplotype between donor and recipient)
Usual criteria for HSCT:
- ECOG ≤ 2
- No severe and uncontrolled infection
- Cardiac function compatible with high dose of cyclophosphamide
- With an adequate organ function ASAT and ALAT ≤ 3N, conjugated bilirubin ≤ 2N (or total bilirubin ≤ 2N if not available), clearance creatinine ≥ 50ml / min
With health insurance coverage
Women of childbearing potential and men must use contraceptive methods during their participation to the research and for 12 months and 6 months after the last dose of cyclophosphamide, respectively.
Having signed a written informed consent

NB: The authorized contraceptive methods are: For women of childbearing age and in absence of permanent sterilization:

oral, intravaginal or transdermal combined hormonal contraception,
oral, injectable or transdermal progestogen-only hormonal contraception,
intrauterine hormonal-releasing system (IUS),
sexual abstinence (need to be evaluated in relation to the duration of clinical trial and the preferred and usual lifestyle of the participants).

For men in absence of permanent sterilization: sexual abstinence, condoms.

Individuals must meet all of the inclusion criteria as verified at the screening / inclusion visit to be eligible to participate at the study.

Exclusion criteria

Patients:

With morphologic evidence of clonal evolution (patients with isolated bone marrow cytogenetic abnormalities are also eligible excepted chromosome 7 abnormalities and complex karyotype).
With seropositivity for HIV or HTLV-1-2 or active hepatitis B or C 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
Yellow fever vaccine and all others live virus vaccines within 2 months before transplantation and during the research
With uncontrolled coronary insufficiency, recent myocardial infarction < 6-month, current manifestations of heart failure according to NYHA (II or more), ventricular ejection fraction <50%
With renal failure with creatinine clearance <50ml /min
Any contraindication mentioned in the SmPC and the Investigator's brochure of all medicinal products planned to be used in the trial including conditioning regimen, GVHD prophylaxis, prevention of EBV reactivation, infection prophylaxis
Known allergy or intolerance to all medicinal products and/or excipients planned to be used in the trial including conditioning regimen, GVHD prophylaxis, prevention of EBV reactivation, infection prophylaxis, according to Investigator's brochure and SmPC.
Who have any debilitating medical or psychiatric illness, which precludes understanding the inform consent as well as optimal treatment and follow-up
Under legal protection (tutorship or curatorship)
Under state medical aid
Participation to another interventional trial on a medicinal product or cell therapy