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Bone-marrow stem cell transplant with post-transplant cyclophosphamide for refractory or relapsed severe aplastic anemia in patients over 40

Evaluation of an Optimized Allogeneic Hematopoietic Stem Cell Transplantation Protocol With Post-transplant Cyclophosphamide in Patients Aged 40 to 60 Years Old With Acquired Aplastic Anemia Refractory or in Relapse After Immunosuppression

Phase 2 Interventional Assistance Publique - Hôpitaux de Paris · NCT06646497

This trial tests whether bone-marrow allogeneic stem cell transplants using post-transplant cyclophosphamide can lower graft-versus-host disease and improve outcomes in patients aged 40–60 with refractory or relapsing severe aplastic anemia after first-line immunosuppression.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment52 (estimated)
Ages40 Years to 60 Years
SexAll
SponsorAssistance Publique - Hôpitaux de Paris Academic / other
Drugs / interventionscyclophosphamide
Locations26 sites (Paris, France and 25 other locations)
Trial IDNCT06646497 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional trial of allogeneic hematopoietic stem cell transplantation using marrow as the graft source together with post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prevention. The approach is offered to patients aged 40–60 with severe aplastic anemia that is refractory or relapsed after at least six months of standard immunosuppressive therapy. Eligible donors include matched sibling, 10/10 matched unrelated, or haploidentical relatives, and donor-specific antibodies must be below a defined threshold. The protocol aims to apply a PTCy strategy across donor types to reduce GvHD-related deaths that have historically limited transplant success in this age group.

Who should consider this trial

Good fit: Ideal candidates are adults aged 40–60 with acquired severe idiopathic aplastic anemia who remained refractory or relapsed after at least six months of ATG plus cyclosporine with eltrombopag, have an approved donor (matched sibling, matched unrelated, or haploidentical), acceptable organ function, ECOG ≤ 2, no uncontrolled infection, and no significant donor-specific antibodies.

Not a fit: Patients without a suitable donor, with donor-specific antibodies above the required threshold, severe organ dysfunction, uncontrolled infection, or outside the 40–60 age range are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could substantially reduce GvHD and improve survival and cure rates for older patients with refractory or relapsing severe aplastic anemia.

How similar studies have performed: Post-transplant cyclophosphamide has markedly reduced GvHD rates in haploidentical and other transplant settings, but its specific efficacy in older refractory/relapsed severe aplastic anemia is not yet well established.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Individuals meeting any of the exclusion criteria as verified at the screening / inclusion visit will be ineligible to participate at the study.

Where this trial is running

Paris, France and 25 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Aplastic AnemiaRefractory/relapse idiopathic anemiaIdiopathic aplastic anemiaHematopoietic stem cell transplantationPost-transplantation cyclophosphamide
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.