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

NCT06646497 | Recruiting Phase 2 DMC

• 1 other identifier: APHP230832
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 26

Brief Summary

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".

Conditions

Aplastic Anemia

Keywords

Refractory/relapse idiopathic anemia; Idiopathic aplastic anemia; Hematopoietic stem cell transplantation; Post-transplantation cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• GRFS (Graft Versus Host Disease (GvHD) and Relapse/rejection-Free Survival)

  GRFS is a composite right-censored endpoint, defined as the time from HSCT to the first of the following events: * primary graft failure, defined as the absence of engraftment from aplasia at day 60 after graft (D0) (i.e., persistence of neutrophils\< 500 AND platelets \< 20 Giga/L) * secondary graft failure, defined as the reoccurrence of aplasia after engraftment (defined as both occurrence of neutrophils\< 500 for 3 days and platelets \< 20 Giga/L for 7 consecutive days) * grade 3-4 acute GVHD, according to the MAGIC CONSORTIUM 2016 * severe chronic GVHD, according to the NIH classification * death, whatever the cause

  2 years after transplantation

Secondary Outcomes (45)

• Neutrophil engraftment

  At day 100

• Platelets engraftment

  At day 100

• Absolute number of neutrophils

  At 1 month

• Absolute number of neutrophils

  At 3 months

• Absolute number of neutrophils

  At 6 months

Study Arms (1)

Allogeneic hematopoietic stem cell transplantation Stem cell source only Bone Marrow

EXPERIMENTAL

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

Interventions

Allogeneic hematopoietic stem cell transplantation Stem cell source only Bone Marrow BIOLOGICAL

1. Conditioning regimen Thymoglobulin (0.5/mg/kg à D-9, 2 mg /kg at D-8 and 2.5 mg/kg à D-7), Fludarabine (30mg/m2/day i.v: day -6 to day -2), pre-transplant, Cyclophosphamide (14.5 mg/kg/day i.v: day -6 and day -5), and Total Body Irradiation (2 Gray on day -1). 2. Stem cell source Bone Marrow only. Target of 4 × 10\^8 nucleated cells/kg recipient body weight. Granulocyte colony stimulating factor is given subcutaneously starting on day +5 at 5 mg/ kg/day until the absolute neutrophil count is greater than 1.5 × 10\^9/L for 3 days. 3. GVHD prophylaxis Cyclophosphamide 50 mg/Kg/day at D+3 and D+4. Tacrolimus (0,2 à 0,3 mg/kg/day per os divided into 2 doses or 0.05 to 0.1 mg/kg/d IVSE) and mycophenolate (MMF) will begin from D+5. In absence of GvHD, MMF will be stopped between D35 and D45 and Tacrolimus at day 365. 4. Prevention of EBV reactivation Rituximab 150mg/m2 intravenously at Day+5 post HSCT (except patients and their donor with EBV serology and EBV PCR negative).

Allogeneic hematopoietic stem cell transplantation Stem cell source only Bone Marrow

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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,

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (26)

Saint Louis hospital

Paris, France, 75010, France

RECRUITING

CHU Amiens

Amiens, France

RECRUITING

CHU Angers

Angers, France

RECRUITING

CHU Besançon

Besançon, France

RECRUITING

CHU Bordeaux

Bordeaux, France

RECRUITING

CHU Caen

Caen, France

NOT YET RECRUITING

HNIA Percy

Clamart, France

RECRUITING

Hôpital d'Estaing

Clermont-Ferrand, France

RECRUITING

Hôpital Henri Mondor AP-HP

Créteil, France

NOT YET RECRUITING

CHU Grenoble Alpes

Grenoble, France

RECRUITING

CHU Lille

Lille, France

NOT YET RECRUITING

CHU Limoges

Limoges, France

RECRUITING

CHU Lyon Sud

Lyon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

NOT YET RECRUITING

CHU Montpellier

Montpellier, France

RECRUITING

CHRU Nancy

Nancy, France

RECRUITING

CHU Nantes

Nantes, France

RECRUITING

CHU Nice

Nice, France

RECRUITING

Hopital Necker - APHP

Paris, France

RECRUITING

Hôpital La Pitié Salpêtrière AP-HP

Paris, France

NOT YET RECRUITING

CHU Poitiers

Poitiers, France

RECRUITING

CHU Rennes

Rennes, France

NOT YET RECRUITING

Henri Becquerel

Rouen, France

NOT YET RECRUITING

CHU Saint Etienne

Saint-Etienne, France

RECRUITING

CHU Strasbourg

Strasbourg, France

RECRUITING

CHU Toulouse

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Central Study Contacts

Régis Peffault de Latour, MD PhD

CONTACT

142385073; regis.peffaultdelatour@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A phase II multicenter, national, prospective, single-arm trial

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: October 17, 2024
• Study Start: January 24, 2025
• Primary Completion (Estimated): January 24, 2030
• Study Completion (Estimated): January 24, 2030
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

FR (26)