CMV Clinical Trial
Official title:
Expansion of Virus-Specific Lymphocytes for Cell Therapy in Immunosuppressed Patients Who Underwent Bone Marrow Transplantation.
Infections and reactivation of human cytomegalovirus (CMV), adenovirus, Epstein-barr and polyoma virus infections are frequent causes of morbidity and mortality and are a source of serious complications in patients undergoing allogeneic bone marrow transplantation. In this project we will prepare specific T lymphocytes from blood donor, select cells CMV-specific by interferon gamma capture and treat patients with CMV viral infections. These cells will be used as antiviral therapy in transplanted patients whom do not respond to conventional therapies or in patients whose conventional therapy may be toxic in the context of transplantation. In this context, CMV reactivation can lead to serious complications in patients, such as irreversible neurological changes, pulmonary, gastrointestinal and ophthalmologic complications, among others, in addition to prolonged hospitalizations, leading to significant morbidity and mortality , both in the health sector public as private. This project may represent an important therapeutic modality using cell of the shelf as a source of therapy for different patients and contributing to reduced morbidity / mortality after transplantation, as well as a reduction in the hospitalization period.
The proposed clinical trial is a phase I single-arm infusion study of cytomegalovirus (CMV)-specific lymphocytes derived from buffy-coat derivatives of platelet donors (ImmuneCellVir-I). T lymphocytes are expanded, stimulated with peptide (pp65) from the viral capsid and selected according to interferon-γ (INF-γ) production in response to the stimulus. After selection, the lymphocytes will be frozen and released for infusion into recipients according to HLA compatibility, result of aerobic/anaerobic cultures and special microorganisms/fungi, endotoxin, donor serological assays, PCR for CMV, EBV and B19 of the product, NAT HCV, HIV, HBS and HTLV-1/2 of the product, and results of impurity and potency tests of the product. The main objective of the study is to evaluate the safety and tolerability of Cytomegalovirus (CMV)-specific Lymphocyte infusion in patients with CMV infection who do not respond to conventional therapies or whose pharmacological therapy may be toxic in the post-transplant context. As secondary outcome to determine the effectiveness of the infusion of CMV-specific lymphocytes The main benefit to potential participants is the treatment of cytomegalovirus infection for patients who are refractory or intolerant to the established drug treatment. Furthermore, the infusion of CMV-specific lymphocytes could potentially help in the immune reconstitution of patients. The expectation is that, with this therapeutic modality, it will be possible to treat patients who have no other treatment alternative. While, the known possible risks are related to cryopreserved allogeneic product infusion reactions and potential risk of graft versus host disease. The possible mechanism of action of this therapy would be through the infused CMV-specific donor cells that would recognize the CMV-infected cells in the patient. CD4 T lymphocytes amplify the immune response by secreting cytokines, CD8 T lymphocytes attack CMV-infected cells, releasing perforins and granzymes. Cytomegalovirus (CMV)-specific lymphocytes will be administered intravenously. Patients will receive therapy containing a total amount of 1x106 CMV-specific T lymphocytes, equivalent to a 1-2x104 dose/kg of recipient weight, which can be repeated on up to 2 occasions with a minimum interval of 2 weeks between infusions, if the patient persists with the presence of inclusion criteria in the study. The trial will be performed in accordance with protocol, good clinical practice and regulatory requirements. At this time, it is not possible to state that all research participants will benefit directly from this study. However, its development will allow a better knowledge of this cellular therapy, allowing an improvement of the protocol and greater efficiency in future protocols to be carried out. It is expected that the proposed treatment generates at least a better quality of life for research participants, with a decrease in complications resulting from the disease. Infusion reactions, development of graft versus host disease (GvHD) and Immunogenicity The primary outcomes of safety of ImmuneCellvir -I will be verified in the patients that will be followed during infusion and 7 consecutive weeks after infusion, and also 100, 180 and 365 days. After cell infusion, patients will be monitored for vital signs (mmHg), pulse rate and blood oxygen level every 15 minutes and must be instructed to contact the study team for any unusual symptoms. After infusion, will be 6 visits (1/week) and 100 days, 6 months and 1 year, after infusion. Patients will be followed for clinical signs and symptoms of acute and chronic GvHD , as gastrointestinal tract alterations, skin, eye, liver, musculoskeletal and lung changes. Patient will be tested for 7 weeks for Bilirubin (μmol/L), Alkaline phosphatase (U/L), Gamma-glutamyl Transferase (U/L) , glutamic-oxaloacetic transaminase/ glutamic pyruvic transaminase (U/L), blood cells count (cells/mm3), creatinine (mg/dL), urea(mg/dL), Serum level of tacrolimus/cyclosporine (mg/dL). For Immunogenicity will be measured the development of anti Human Leukocyte Antigen antibodies in the patient. The secondary outcome will be measured by the evaluation of clinical symptoms score, level of CMV copies and anti-CMV response. The secondary or exploratory outcome will be performed for as indicative of efficacy. This outcome will be reported as a score of clinical symptoms, comparing the symptoms before and after the infusion. Laboratorial tests will be performed for 7 consecutive weeks after the infusion to demonstrated the patient clinical improvement as the rate of CMV viral load (copies/mL), rate of anti-CMV response in the peripheral blood of patients by ELISpot (IFN-y spots/10x6cells). The patients can be also evaluated for specific exams (if required) depend on the site of infection as computed tomography, colonoscopy, eye fundus examination and biopsy. In addition, assays to determine cell biodistribution as chimerism (%) after infusion will be performed. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Enrolling by invitation |
NCT04101136 -
Effect of Atorvastatin on Subclinical Atherosclerosis
|
N/A | |
Recruiting |
NCT06001320 -
De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Trans Recip
|
Early Phase 1 | |
Completed |
NCT01923766 -
Cytotoxic T Cells to Prevent Virus Infections
|
Phase 1 | |
Not yet recruiting |
NCT05969743 -
Letermovir Prophylaxis for Cytomegalovirus (CMV) in Patients With Graft-versus-host Disease
|
Phase 2 | |
Recruiting |
NCT01011712 -
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
|
||
Recruiting |
NCT06034925 -
Maribavir vs. Valganciclovir for CMV Prophylaxis in High-Risk Kidney Transplant Recipients
|
Phase 4 | |
Completed |
NCT04840199 -
A Study to Evaluate the Anti-inflammatory Effects of Letermovir (Prevymis) in Adults With Human Immunodeficiency Virus (HIV)-1 and Asymptomatic Cytomegalovirus (CMV) Who Are on Suppressive Antiretroviral Therapy, Plus Its Effect on Chronic Inflammation, HIV Persistence and Other Clinical Outcomes.
|
Phase 2 | |
Terminated |
NCT03502161 -
Clinical Evaluation of the QuantiFERON CMV Assay
|
||
Not yet recruiting |
NCT06211543 -
Letermovir (LMV) Prophylaxis in CMV-seronegative Allogeneic Stem Cell Transplant Recipients With CMV Seropositive Donors: an Exploratory Study From Spanish GETH/TC Centers
|
||
Recruiting |
NCT04056533 -
Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy
|
Phase 2 | |
Not yet recruiting |
NCT04280380 -
Cytomegalovirus Infection in Critically Ill Patients and Patients Receiving Anticancer Therapy
|
||
Active, not recruiting |
NCT03924219 -
CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients
|
||
Not yet recruiting |
NCT06453460 -
Prospect Eval of Efficacy of CMV-TCIP Direct Letermovir Prophylax After Allogen Hemato Cell Transpla
|
Phase 2 | |
Completed |
NCT02694484 -
Search Cytomegalovirus in Healthy Volunteers Stools Samples Selected as Potential Donor for Fecal Microbiota Transplant
|
N/A | |
Recruiting |
NCT04017962 -
A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection
|
Phase 2 | |
Terminated |
NCT03570411 -
Evaluating the Clinical Utility of the T-SPOT.CMV Assay for the Prediction of CMV Reactivation Among Pediatric Patients Undergoing Hematopoietic Cell Transplant
|
||
Enrolling by invitation |
NCT04392297 -
Clinical and Immunological Features of the CMV Infection Atypical Course in Immunocompetent Individuals
|
||
Completed |
NCT00872703 -
Does Normal Brain Imaging Predict Normal Neurodevelopmental Outcome in Fetuses With Proven Cytomegalovirus Infection?
|
N/A | |
Active, not recruiting |
NCT01945814 -
Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL)
|
Phase 1 | |
Recruiting |
NCT05041426 -
Letermovir for CMV Prevention After Lung Transplantation
|
Phase 2 |