View clinical trials related to Allogeneic Disease.
Filter by:Despite progress in chemotherapy, targeted therapy and immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-SCT) is still the only curative procedure for some hematological malignancies. The probability of finding a matched sibling donor (MSD) is estimated under the classical 30%, because of the age of patients and their relatives, and a matched unrelated donor (MUD) can take time to identify. Currently in France, 25% of the allo-SCT are performed with an haplo-identical related donor. The Baltimore group developed an approach using haploidentical related donors, RIC, T-replete bone marrow and post-transplant high dose cyclophosphamide (PTCy) in patients with advanced hematological malignancies. PTCy has shown to eradicate alloreactive donor and host T-cells, activated by respective antigens, thereby reducing the incidence of graft versus host disease (GvHD) but delaying hematopoietic recovery. Therefore, the main source of graft is peripheral blood stem cells (PBSC) mobilized by G-CSF in France. Unfortunately, with PBSC we observe a higher cumulative incidence of GvHD (around 50%) and a higher toxicity-related mortality (TRM), especially for recipients >50 years old. The co-transplantation of Mesenchymal Stem Cells (MSC) at the time of transplantation has previously shown a double interest in GvHD immunomodulation and hematopoiesis support. Pre-clinical studies (in mice) have shown that mesenchymal stromal cells (MSCs) from Wharton's Jelly reduce the incidence of GvHD when the infusions are weekly repeated. We propose a phase I clinical trial to find the maximum tolerated dose (MTD) of a weekly infusion of WJ-MSC administered as GvHD prophylaxis and as a support for a faster hematological reconstitution after haplo-identical allo-SCT.
People who undergo allogeneic bone marrow transplant for blood cancers receive the highest chemotherapy doses possible that humans can receive and still survive. As a result, they have devastating side effects during the procedure and for many years afterwards. Damage to organs and muscles cause long-lasting physical weakness and the psychological experience is severe enough to be termed 'post traumatic stress disorder' that also lasts for many years. These effects are worsened by the fact that most Canadians live several hours away from treatment and transplant centers, leaving them entirely on their own to manage these difficult long term effects. The APOLLO team will perform a qualitative study to learn the experiences of people undergoing allogeneic bone marrow transplant while they receive access to a supportive care computer 'app' and telephone support from nursing, exercise and nutrition experts. In this way, the APOLLO team will learn the most helpful type and timing of supportive care from those who know best.
Currently, transplantation centers across North America generally do not offer longitudinal rehabilitation programs and research is urgently needed to test the acceptability and effectiveness of these programs using innovative delivery strategies that have the potential for future scalability and to understand the associated costs. Through a strong collaboration between the PM Cancer Rehabilitation and Survivorship (CRS) and alloBMT teams, the principal investigators developed an innovative multicomponent rehabilitation intervention for patients undergoing alloBMT (CaRE-4-alloBMT). CaRE-4-alloBMT uses a person- centred strategy and a multidimensional approach targeting physical activity, nutrition, psychosocial distress and promoting self-management skills. Innovative components of CaRE-4-alloBMT include:1) Individualized progressive exercise prescriptions developed and monitored by CRS registered kinesiologists and supported with a web/mobile application (Physitrack) that allows customizable exercise prescriptions, tracking of exercise completion, and video tutorials; 2) Individualized nutrition plans and stepped stratified care (education, counselling, intervention) based on nutritional status and delivered by registered dietitians (alloBMT and CRS). 3) On-line e-modules (developed in collaboration with PM Oncology Education) provide interactive education to promote self-management skills on crucial topics; 4) Remote monitoring using FitbitTM devices to monitor patients physical activity, caloric intake, and sleep for duration of the program; 5) Remote clinical support: Pre/Post discharge, patients will have scheduled (PHS) remote check-ins and health coaching sessions with a member of the CRS team (phone or MS Teams video). Objectives: i) To test the feasibility and safety of CaRE-4-alloBMT plus standard best practice cancer care compared to standard best practice cancer care alone; ii) To assess the preliminary efficacy of CaRE-4-alloBMT on physical function, disability, nutritional status, distress, QoL, healthcare utilization, and survival and estimate program return on investment.
Phase III randomized double-blinded trial designed to compare the efficacy of the addition of MTX to current standard acute GVHD first-line treatment with corticosteroids. The protocol will use a novel endpoint for benchmarking interventions based on a composite primary endpoint of GVHD-free and corticosteroids-free survival. The primary endpoint of the trial will be the assessment of a composite endpoint of graft-versus-host disease-free and corticosteroids-free survival at 12 months after randomization
Scientific context Epstein-Barr virus has a causal role in the pathogenesis of multiple distinct lymphomas. Post-transplant lymphoproliferative diseases (PTLD) are the most frequent EBV-induced proliferations. PTLD after allogeneic stem cell transplantation has an incidence lower than 5% but may increase up to 10-20% in patients with established risk factors. EBV-DNAemia is predictive of EBV-PTLD and is routinely performed using qPCR on whole blood. Preemptive therapeutic strategies with anti-CD20 antibody are used when patients are above a defined EBV-DNAemia threshold. This approach remains limited since it does not discriminate between an EBV-induced lymphoproliferation (latent cycle) and/or a replicating virus (replicative cycle). Epigenetic modifications plays a central role in regulating the switch from latent to lytic gene expression. Specific DNA modifications can be regarded as molecular signatures for EBV genomes associated with the status of the viral infection (latent vs lytic). Accordingly, these signatures may be envisioned as a potent tool to characterize the state of the viral infection in vivo. Description of the project Our primary objective is to estimate the respective percentages of EBV-lytic and EBV-latent genomes (proliferating cells) in patients presenting with a high EBV-DNAemia after allogeneic stem cell transplantation HSCT by analysing the epigenetic modifications of EBV genome on specific sites. Our secondary objectives are i) to determine risk factors associated with each "latent versus lytic EBV" profiles and ii) to correlate the "latent versus lytic EBV" profiles with response to rituximab infusion and patient outcomes. For this purpose, a retrospective study (n=80) and a prospective study (estimation n=58) will be established. The different steps of this project are: 1. To study epigenetic modifications. The laboratory is developing a new approach to distinguish between latent and lytic genomes. 2. To realize quantitative analysis by RT-PCR of different EBV transcripts specific of the latent or of the lytic phase of the virus This method will be applied on RNA extracted from patient blood samples with elevated EBV viral load, under condition preserving RNA integrity. The results will be validated on a prospective cohort of HSCT patients (n=58) (Saint-Antoine Hospital and La Pitié-Salpêtrière Hospital). 3. To perform quantitative analysis of EBV genomes in plasma, saliva and total blood samples by current routine procedures In addition to total blood samples, plasma and saliva will be collected since free viral particles are known to accumulate in these biological fluids upon EBV reactivation. These samples will be treated by normalized procedures that are routinely used in the medical virology laboratory to quantify EBV in human samples. Expected results By establishing a simple method for studying epigenetic modifications of EBV genomes, we expect to understand the significance of high EBV viral load and the pathophysiology of post-HSCT PTLD. We aim to distinguish between the latent / lytic profiles of HSCT patients and to correlate their respective risks for developing PTLD. Establishing the epigenetic EBV profile in the post-HSCT setting when facing increase viral load and PTLD will improve our understanding of the biological mechanisms determining EBV-status in post-HSCT. This should improve major medical and economical issues. These results could have a major therapeutic
Hospitalization for allogeneic haematopoietic stem cell transplantation constitutes a particular time in the management of patients with malignant hemopathies both for the patient, for his entourage or for the nursing staff. For the patient, the strict protective isolation set up during this period is a source of isolation in the broad sense and is associated with an escape from external events and society. It also constitutes a physical barrier (mask, charlotte, surblouse and overshoes worn by caregivers or visitors) and even psychological in relations with relatives. Moreover, this period is also difficult because of the possible complications of conditioning (mucositis, transit disorders, fever ...) and allograft itself (graft versus host disease, no transplant, relapse disease…). The patient may be weakened and diminished, which can give a feeling of helplessness and uselessness to the family. Finally, this therapy can have serious physical and psychological consequences for the patient and his entourage (especially in the case of family allograft) who do not always have the possibility to express themselves verbally. Published studies in hematology report depressive, anxious and post-traumatic stress disorders in patients and relatives during allogeneic haematopoietic stem cell transplantation. It is therefore important to reduce these symptoms, particularly those related to the cut-off during hospitalization for allogeneic haematopoietic stem cells. Over the last decade or so, the logbook has been used in some resuscitation services in intubated patients, with the main objective of filling the "memory gap" mentioned by the intubated patients when they woke up and limiting the trauma associated with this Cut in the world corresponding to the sedation period. For this purpose, the use of a logbook in Hematology, by analogy with what is used in the resuscitation services, could be a means of limiting the psychological complications related to the allograft.