CMV-Specific CTLs for CMV Infection
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: New York Medical College
Must not be taking: Steroids, Thymoglobulin, Alemtuzumab, others
Disqualifiers: Acute GVHD, Poor performance, HIV, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults (CAYA) with refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD
Do I need to stop my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients with certain conditions or treatments, like those receiving steroids or certain immunosuppressive therapies, are excluded from participation.
What data supports the effectiveness of the treatment CMV-specific CTLs for CMV infection?
Research shows that CMV-specific cytotoxic T cells (CTLs) can help control CMV infection after stem cell and bone marrow transplants by reducing the risk of severe CMV disease. Patients with a strong CMV-specific CTL response were less likely to develop CMV-related complications, suggesting that this treatment can be effective in managing CMV infections.12345
Is CMV-specific CTL treatment safe for humans?
How is the CMV-specific CTL treatment different from other treatments for CMV infection?
The CMV-specific CTL treatment is unique because it uses the patient's own immune cells, which are trained to specifically target and destroy CMV-infected cells, offering a personalized approach that can be more effective in reconstituting immunity in immunocompromised patients compared to standard antiviral drugs.12456
Research Team
Mitchell S Cairo, MD
Principal Investigator
New York Medical College
Eligibility Criteria
This trial is for children, adolescents, and young adults aged 0.1 to 30.99 years with refractory CMV infection after a stem cell or organ transplant, or those with primary immunodeficiencies. Participants must have tried antiviral therapy without success or cannot tolerate it due to side effects like low white blood cell counts or kidney issues.Inclusion Criteria
Obtained informed consents by donor or donor legally authorized representative prior to donor collection
I have a family donor who matches me and is CMV positive or has a T-cell response to CMV.
I am between the ages of 0 and 79.
See 6 more
Exclusion Criteria
I have been diagnosed with HIV.
Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory CMV infection
Any medical condition which could compromise participation in the study according to the investigator's assessment
See 11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
CMV specific CTLs are administered to patients with refractory CMV infection
Up to 5 doses
1 visit per dose (in-person)
Follow-up
Participants are monitored for safety and effectiveness after each infusion
12 weeks after each infusion
Weekly monitoring (in-person or virtual)
Treatment Details
Interventions
- Viral Specific Cytotoxic T-Lymphocytes (Virus Therapy)
Trial OverviewThe study tests the use of virus-specific cytotoxic T-lymphocytes (CTLs) in patients who haven't responded well to standard treatments for CMV infections post-transplantation. These CTLs are developed using a special system and aim to fight off the persistent infection.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Refractory CMVExperimental Treatment1 Intervention
Patients with refractory CMV will be given one dose of CMV specific CTLs. HLA matched donors will get Dose 2.5 × 10(4) CD3/kg recipient weight; HLA mismatched will get 0.5x10(4) CD3/kg recipient weight. Additional doses may be given for a total of 5 doses if patients do not have a response to the first dose with a reduction in viral load to normal limits.
Viral Specific Cytotoxic T-Lymphocytes is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Viral Specific Cytotoxic T-Lymphocytes for:
- Refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT)
- Primary immunodeficiencies (PID)
- Post solid organ transplant
🇪🇺 Approved in European Union as CMV-specific CTLs for:
- Refractory cytomegalovirus (CMV) infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT)
- Primary immunodeficiencies (PID)
- Post solid organ transplant
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana UniversityIndianapolis, IN
Nationwide Children's HosptialColumbus, OH
Children's Hospital Los AngelesLos Angeles, CA
Medical College of Wisconsin/Children's Hospital of WisconsinMilwaukee, WI
More Trial Locations
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Who Is Running the Clinical Trial?
New York Medical College
Lead Sponsor
Trials
73
Patients Recruited
8,700+
Children's Hospital of Philadelphia
Collaborator
Trials
749
Patients Recruited
11,400,000+
Medical College of Wisconsin
Collaborator
Trials
645
Patients Recruited
1,180,000+
Indiana University
Collaborator
Trials
1063
Patients Recruited
1,182,000+
Washington University School of Medicine
Collaborator
Trials
2027
Patients Recruited
2,353,000+
Johns Hopkins University
Collaborator
Trials
2366
Patients Recruited
15,160,000+
Children's Hospital Los Angeles
Collaborator
Trials
257
Patients Recruited
5,075,000+
Nationwide Children's Hospital
Collaborator
Trials
354
Patients Recruited
5,228,000+
University of California, San Francisco
Collaborator
Trials
2636
Patients Recruited
19,080,000+
References
Rapid monitoring of immune reconstitution after allogeneic stem cell transplantation--a comparison of different assays for the detection of cytomegalovirus-specific T cells. [2013]Cytotoxic T cells (CTLs) play an important role in controlling cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The purpose of this study was to compare four different assays to detect CMV antigen-specific T cells for the monitoring of CMV-specific immune reconstitution after HSCT.
Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. [2021]The high rate of severe cytomegalovirus (CMV) disease after bone marrow transplantation (BMT) is related to the profound immunodeficiency posttransplant. Because cytotoxic T lymphocytes (CTL) have been implicated in resistance to viral infections, we examined the restoration of the CMV-specific CTL response in 20 patients who received bone marrow from HLA-matched, CMV-seropositive donors. Blood specimens were obtained from patients at 1, 2, and 3 months after BMT and from the donors on a single occasion. Peripheral blood mononuclear cells were cocultured with CMV-infected donor-derived fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected and uninfected autologous or HLA-mismatched fibroblasts. Cytolytic activity was detected in all 20 donors, with specificity for autologous CMV-infected targets demonstrable in 17 (median CMV-specific lysis at an effector:target ratio of 15:1 was 32%, range 18% to 83%). Specific lysis was mediated by CD8+, class I-restricted T cells, as shown by inhibition with anti-class I monoclonal antibody and by selective depletion of effector cells. By contrast, CMV-specific CTL were detected in only 10 of 20 patients after BMT (median lysis 29% at 3 months post-BMT). None of these 10 patients developed CMV pneumonia, whereas 6 of the 10 patients with an undetectable CMV-specific CTL response after BMT died with CMV pneumonia. These results demonstrate that restoration of CMV-specific CTL responses may require an extended time period after BMT in some patients, and that such patients are at increased risk of developing severe CMV disease. Approaches to reconstitute CMV immunity in BMT patients by adoptive transfer of CMV-specific CD8+ CTL clones derived from the bone marrow donor are now being pursued.
CMV-specific T cell therapy. [2007]Human cytomegalovirus (CMV) infection continues to be one of the most important and life threatening complications after allogeneic stem cell transplantation (SCT). The reconstitution of CMV-specific T cell responses after SCT has been demonstrated to be protective against the development of CMV disease. To improve T cell immunity against CMV in bone marrow transplant patients, different strategies were explored. On one hand, CMV-specific T cells can be selected from the donor, and can be transferred to the patient without any further in vitro expansion. On the other hand, CMV-specific T cells can be activated and expanded in vitro by stimulation with antigen presenting cells (APCs) loaded with specific proteins or peptides. Here, we review the therapeutic application of CMV-specific T cells to fight CMV infection.
Definition of human cytomegalovirus-specific target antigens recognized by cytotoxic T cells generated in vitro by using an autologous lymphocyte system. [2006]We developed an in vitro system for the generation of human cytomegalovirus (CMV)-specific cytotoxic T cells (CTL) that avoids the necessity of constituting a panel of HLA-typed fibroblasts. Autologous donor leucocytes were coated with CMV antigens and were used as both stimulator and target cells. With the use of this system, CMV-specific effector cells were efficiently generated from seropositive but not seronegative donors. These CMV-specific effectors were HLA-restricted and had characteristics of T cells. Maximum lymphoproliferation preceded the appearance of maximum CTL activity by 3 to 4 days, and a close correlation was seen between both activities. Mouse anti-CMV monoclonal antibodies were used in blocking experiments in an attempt to define target antigens recognized by CMV-specific cytotoxic lymphocytes. Monoclonal antibodies directed against an early CMV membrane antigen, against neutralization epitopes, or against nuclear inclusion body protein all specifically inhibited CMV-sensitized effector cell activity but did not affect influenza virus-specific lysis. Monoclonal antibodies directed against a normal cell determinant or against poliovirus did not affect CMV-specific CTL activity. CMV-immune cytotoxic T cells could be consistently and specifically inhibited in their lytic activity by pretreating antigen-coated target cells with monoclonal antibodies directed against CMV-related proteins.
Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load. [2006]The role of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTLs) and T helper cells (Th) in controlling CMV infection, as detected by antigenemia assay and polymerase chain reaction (PCR) in blood leukocytes, and CMV disease was investigated in 20 renal transplant recipients. Within 3 months after transplant, CMV-specific CTL and Th responses were demonstrable in 11 (55%) and 15 (75%) patients, respectively; CMV infection was detected by antigenemia and PCR in 19 (95%) patients each. During the month of first CMV detection, there was an inverse correlation between CTL response and antigenemia at >/=20 positive cells/105 leukocytes (P=.007) but no association with lower antigenemia levels or PCR positivity. CMV disease developed in 7 (35%) patients and was associated with high-level antigenemia but was inversely correlated with detection of CTLs (P=.04). After renal transplantation, CMV-specific CTLs limit the systemic virus load as reflected by antigenemia levels and thereby mediate protection from CMV disease.
Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised patients. [2005]Cytomegalovirus (CMV) reactivation in immune compromised patients such as those undergoing hematopoietic progenitor cell transplantation (HPCT) and those with HIV infections can cause severe morbidity and mortality despite treatment with appropriate antiviral agents. The recovery of Cytomegalovirus (CMV) specific cytotoxic T lymphocytes (CTL) plays an important role in the reconstitution of CMV specific immunity in immunocompromised patients. Recent studies have reported that CMV reactivation can be successfully treated by adoptive transfer of CMV-specific T cell clones from CMV seropositive donors expanded in vitro with CMV infected fibroblasts or lysates of CMV infected cells. Other studies have used immune dominant CMV proteins or peptides to expand CMV-specific cytotoxic T lymphocytes. This review describes the clinical manifestations of CMV disease in immunocompromised patients, recent advances of antiviral therapy for CMV disease, the principals of the induction of cellular immune response to CMV, and the clinical application of CMV immunotherapy.
Robust Production of Cytomegalovirus pp65-Specific T Cells Using a Fully Automated IFN-γ Cytokine Capture System. [2022]Cytomegalovirus(CMV)-related diseases are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). CMV-specific cytotoxic T lymphocytes (CMV-CTLs) have been reported as an alternative to antiviral drugs that provide long-term CMV-specific immunity without major side effects. However, their application has been limited by the prolonged manufacturing process required.
Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation. [2014]Cytomegalovirus (CMV)-specific CD8(+) cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear.
Pharmacotherapy versus T lymphocytes for CMV. [2021]In this issue of Blood, Blyth et al report a phase 2 study in 50 allogeneic hematopoietic stem cell transplant (HSCT) recipients who received donorderived cytomegalovirus (CMV)-specific cytotoxic T cells (CTLs) and compare outcomes with a group of concomitant controls who were transplanted at the trial centers but who did not receive CTLs.