Clinical Research Directory

Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation

This is a prospective, single-arm, phase II study. Patients will be treated with an allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on patient- and disease-related risk.

Cardiovascular Complications in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) represents a major therapeutic strategy for malignant hematologic diseases, with the number of procedures steadily increasing in France each year. Conditioning and maintenance regimens carry a risk of both short- and long-term cardiotoxicity, leading to serious cardiovascular events including acute coronary syndrome (ACS), cardiac dysfunction, arrhythmias, pulmonary hypertension, and pericardial effusion. The pathophysiology of cardiotoxicity in HSCT patients remains poorly understood. It is therefore crucial to investigate underlying mechanisms and identify predictive factors of cardiotoxicity in order to provide appropriate cardiological follow-up and management. Current European Society of Cardiology guidelines recommend routine monitoring of HSCT patients with echocardiography and cardiac biomarkers (NT-proBNP, troponin), although these recommendations are based on small-scale studies. The cardiodepressor factor DPP3 has shown promising results in cardio-oncology, with a causal role in anthracycline-induced cardiac dysfunction. Its role in HSCT-related cardiotoxicity requires further evaluation. This multicenter study of HSCT recipients will be a valuable resource, enabling a better understanding of the pathophysiology of cardiotoxicity and prognosis. It will highlight imaging (echocardiography, calcium score, supra-aortic Doppler), electrocardiographic, and biological markers (including DPP3) associated with prognosis.

Maintenance Therapy With Selinexor and Azacitidine in TP53 Mutant AML/MDS After Transplantation

This study aims to explore the safety and efficacy of selinexor combined with azacitidine for maintenance therapy in TP53 mutant AML/MDS patients following transplantation.

Immunoglobiulin-specific Prophylaxis of Citomegalovirus Infections in Immunocompromised Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Human cytomegalovirus (CMV) is a globally prevalent, human-specific herpesvirus characterised by a lifelong latency after primary infection, an often asymptomatic reactivation and affecting up to 100% of adults based on region and age. CMV reactivation has serious risks for immunocompromised patients, especially those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In these patients, CMV can lead to graft failure, multiorgan disease, increased risk of other infections, GVHD, post-transplant lymphoproliferative disorders, and higher transplant-related mortality (TRM). Although antiviral prophylaxis, CMV infection occurs in 38-80% of HSCT recipients, but current antiviral drugs are insufficiently effective and they are associated with adverse effects. Furthermore, treatment failure is due to the high genetic variability of CMV. The protective role of virus-specific antibodies remains under debate. Some studies suggest that high neutralizing antibody titers protect transplant recipients from CMV, while others highlight the importance of T-cell responses. However, recent animal studies showed that humoral immunity alone can prevent CMV reactivation, even without T or NK cells. In solid-organ transplant patients, antibody titers ≥480 have been linked to reduced infection, shorter treatment, and full protection from CMV disease. Although the use of anti-CMV immunoglobulin remains controversial, the IRCCS Burlo Garofolo has used it as post-transplant prophylaxis and second-line treatment for over a decade. The main objective of their study was to assess whether CMV-specific immunoglobulin prophylaxis reduces CMV incidence and severity in pediatric HSCT patients. Secondary goals included evaluating its effect on transplant outcomes and its efficacy across different ethnic groups. A population pharmacokinetic (POP/PK) study was also conducted to better understand the drug's distribution and elimination and to identify factors influencing its pharmacokinetics in patients.

Acupoint Application With Herbal Fumigation and Wash for Preventing Diarrhea-induced Perianal Infection in Allo-HSCT Patients

The goal of this clinical trial is to evaluate whether the combination of herbal fumigation and acupoint application can effectively prevent diarrhea in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).The main questions it aims to answer are: Does the combination of herbal fumigation and acupoint application reduce the incidence of diarrhea in allo-HSCT patients? Does this intervention improve patients' quality of life and reduce the risk of perianal infections? Researchers will compare the intervention group (herbal fumigation + acupoint application) to the control group (povidone-iodine warm water fumigation) to determine the effectiveness of the TCM-based approach in preventing diarrhea and related complications. Participants will: Receive either herbal fumigation and acupoint application or povidone-iodine warm water fumigation twice daily, starting from 24h before transplant conditioning until 30 days post-transplantation (Day +30). Undergo daily monitoring of perianal and local skin conditions, as well as diarrhea symptoms, by trained professionals. This study aims to provide evidence for a non-invasive, low-risk TCM approach to improving outcomes for allo-HSCT patients.

Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation

The purpose of this study is to determine if it is possible to treat an infection with a cell-based immunotherapy (therapy that uses the patient's own immune system to treat the infection). This treatment is called adoptive T cell therapy. Another purpose is to learn about the side effects and toxicities of adoptive T cell therapy. Adoptive T cell therapy is an investigational (experimental) therapy that works by using the blood of a donor that has immunity against the virus. The donor cells are collected and then the cells, called T cells, that are capable of defending against the virus are selected out. These selected T cells are then infused back into the patient, to try to give the immune system the ability to fight the infection. Adoptive T cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).

Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome

The goal of this clinical trial is to compare outcomes of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients. The main questions it aims to answer are: * The safety of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years. * The efficacy of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years. Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)

Allogeneic Hematopoietic Stem Cell Transplantation Cohort Study

Clinical observational studies using epidemiologic theories and methods. Through the collection of various clinically relevant data, specific outcomes are evaluated in hematologic transplant patients, providing high quality real-world data for clinical practice, informing public health decision-making, and reducing the burden of disease

Impact of the Use of Allogeneic Hematopoietic Stem Cell Transplantation in Reunion Island Patients: Quality of Life, Determinants of Choices and Financial Repercussions

This project aims to document and analyse - with a three-fold anthropological, psychosocial and economical approach - the consequences of the geographical distance from mainland France on the alloSCT on both patients, their caregivers and the healthcare system. It is organised in 3 working packages (WP).

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide for Rescuing Patients With Graft Failure

Prognosis of patients with graft failure is dismal, and re-transplantation is the sole option for long-term survival. Currently, there is no consensus concerning therapeutic options in patients with primary or secondary (within the 60 days post-transplantation) graft failure and finding a new donor within an acceptable delay is challenging. Literature is poor on the subject while the overall survival of such patients is about 30% at 1 year. This situation thus represents today a very challenging unmet medical need. Recently, haploidentical (haplo) related donor Stem Cell Transplantation (haplo-SCT) have improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy, which targets alloreactive T cells generated early after an HLA-mismatched transplant, sparing regulatory T cells and leaving unaffected the non-dividing hematopoietic stem cells) and standard post-transplant immune suppression with a calcineurin inhibitor (CNI) and mycophenolate mofetil. Our group re-transplanted a patient who experienced two consecutive graft failures and was successfully managed through a third haplo-SCT from her son using PTCy. We then retrospectively collected and analyzed data from 26 primary graft failure patients transplanted between 2011 and 2017 in 15 centers on behalf of French Society for Stem Cell Transplantation and Cell Therapy (SFGM-TC). The study population consisted mainly of patients with primary or secondary (within the 60 days post-transplantation) graft failure who underwent haplo-SCT and received PTCy as graft-versus-host-disease prophylaxis. The 1-year overall survival was about 60% suggesting that this approach might be a valid option in this particular poor clinical situation but now need validation through a phase II multicenter, national, prospective cohort study.

Determination of Factors Involved in the Regulation of Immune Responses After Allogeneic Hematopoietic Stem Cell Transplantation

The study concerns donors and patients receiving allogeneic stem cell haematopoietic transplantation. The aim of the study is to analyse HSC graft content in immune effector T (naive, memory, activated, exhausted) and immunoregulatory cell subtypes (Tregs, iNKT, MDSC) and correlate the results with post-transplant immune reconstitution of those different cell subtypes and clinical events (graft-versus-host-disease, relapse, infections). An ancillary study will focus on the impact of microbiota dysbiosis on post-transplant immune response and regulatory cell subsets.