Expansion of Virus-Specific Lymphocytes for Cell Therapy
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorHospital Israelita Albert Einstein
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be able to provide signed informed consent.
Must be between 18 and 75 years old at the time of signing the consent form
Having undergone allogeneic hematopoietic stem cell transplantation (related, unrelated, haploidentical or cord blood transplant)
Negative pregnancy test for women of childbearing age (non-fertile age defined as post-menopausal over one year, or surgically sterilized); Acceptance of the use of contraceptive methods by sexually active men and women of childbearing age;
Disqualifiers
Patients who do not meet the inclusion criteria
Patients who do not agree to participate in the study or sign the consent form
Patients reporting allergy to murine antibodies or iron-dextran
Patients with grade 3 or 4 graft versus host disease/graft versus host disease in activity/treatment
Trial design
Design model
Single group
Treatments tested in this trial
Lymphocyte infusion (ImmuneCellVir-I)
Combination productInfusion of donor CMV specific cells into patients eligible to the trial
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: Lymphocyte infusionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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 hours2
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 weeks3
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 weeks4
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 montasSecondary outcomes
1
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 weeks2
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 weeks3
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 monthSponsors and contacts
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Source ClinicalTrials.gov