A Phase 1 interventional study of Lymphocyte infusion (ImmuneCellVir-I) in CMV Viremia and CMV, sponsored by Hospital Israelita Albert Einstein. Recruiting at 1 site in Brazil. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-10-24.
Sponsored by Hospital Israelita Albert Einstein · Phase 1, Interventional, and Treatment
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.
57 studies on the registry are indexed under Viremia; 12 are open to participants now.
This study's planned enrollment of 10 is below the median of 87 across 45 interventional studies indexed under Viremia.
Browse Viremia studies →Hospital Israelita Albert Einstein is the lead sponsor of 147 studies on the registry; 32 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with CMV disease or reactivation will be included for receiving donor-CMV-specific cells
Combination Product: Lymphocyte infusion (ImmuneCellVir-I)
Infusion of donor CMV specific cells into patients eligible to the trial
Also known as: CMV-specific cells infusion
Number of patients with immediate infusion reactions
Safety of cytotoxic T cell (CTL) based on patients with grade 3 immediate adverse events that are at least possibly related to the CTL infusion within 3 hours of the CTL infusion, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.
Time frame: 3 hours
Development of Acute graft versus host disease (GvHD)
Number of Patients that present Acute GvHD Grades III-IV \[ Time Frame: 6 weeks\] Safety of cytotoxic T Cell (CTL) will be based on patients with acute GvHD grades III-IV within 6 weeks after the last dose of CTL. Acute GVHD grading will be performed according to NIH criteria (1). Grade 0 represents no acute GvHD. Grade 4 represents the most severe acute GvHD. 1-Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10.
Time frame: 6 weeks
Development of Non-Hematological Adverse events
Number of Patients With Grades 3 Non-hematologic Adverse Events Related to the T Cell Product \[ Time Frame: 6 weeks \] Safety of VSTs based on patients with grade 3 non-hematologic adverse events that are at least possibly related to the CTL infusion within 6 weeks of the last CTL dose, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.
Time frame: 6 weeks
Risk for chronic GVHD [ Time Frame: At 6 and12 months post CTL infusion ]
Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated.
Time frame: 6 to 12 montas
Antiviral activity defined as response to viral load [ Time Frame: 6 weeks ]
Complete response, partial , or no response will be defined and proportion of each outcome will be calculated.
Time frame: 6 weeks
Rate of anti-CMV response improvement in the peripheral blood of participants [ Time Frame: 6 weeks ]
Anti-CMV response will be measured by ELISpot (IFN-y spots/10e6 cells)
Time frame: 6 weeks
Clinical response to CTL infusions [ Time Frame: At 6 weeks and 3 months ]
In cases with CMV disease, clinical response can be evaluated with evaluation of the involved organ with specific exams (if required) as computed tomography, colonoscopy, eye fundus examination and biopsy .
Time frame: 6 weeks and 3 month
Started Jun 2024 (actual). Primary completion is estimated for Jun 2025, 12 months after the start.
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