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

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Oct 16, 2024

Keywords

ClinConnect Summary

This clinical trial, called "APARR," is investigating a treatment option for adults over 40 years old who have severe aplastic anemia (SAA) that hasn’t improved with standard therapies. Aplastic anemia is a serious condition where the body doesn’t make enough blood cells. The trial will focus on a procedure called hematopoietic stem cell transplantation (HSCT), which involves using stem cells to help the body produce blood again. The researchers aim to see if a new method that includes specific strategies to prevent complications can improve patient outcomes, especially since older patients often face higher risks after this treatment.

To be eligible for this trial, participants should be between 40 and 60 years old, have been diagnosed with refractory severe aplastic anemia after at least six months of standard treatment, and have a suitable stem cell donor. Participants must also be in good overall health, without severe infections or heart problems. Those who join the trial can expect to receive the new treatment approach and will be closely monitored by medical professionals throughout the process. It's important to know that the trial is not yet recruiting participants, so enrollment hasn’t started.

Gender

ALL

Eligibility 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.