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This protocol is a phase I study. Patients may be eligible for an infusion of Multi-virus Cytotoxic T Lymphocytes (CTL) if they received a T-cell depleted (TCD) transplant from a related family member or an unrelated donor. Recipients of these types of transplants are severely immune compromised during the early post-transplant period and are more susceptible to certain viruses. The investigators hypothesize that the adoptive transfer of Cytotoxic T Lymphocytes (CTL) against certain viruses: Adenovirus, Cytomegalovirus and Epstein Barr Virus (Ad, CMV, and EBV) will be safe with regard to producing graft versus host disease (GVHD) or other infusion related toxicities.
Within this clinical trial, the investigators will test the hypotheses that the administration of CTLs for prophylaxis against Ad, CMV and EBV in recipients of TCD-HPCT will be safe and well tolerated. Graded doses of Multi-Virus CTL will be administered to recipients of genotypically haploidentical or mismatched unrelated TCD grafts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Multi-Virus CTLs | Experimental | The treatment plan delivers a single dose of Multi-Virus CTL to all patients enrolled on study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cytotoxic T Lymphocytes | Biological | Patients will be studied in cohorts of 3. Eligible patients will receive a single Multi-Virus CTL line infusion 28-100 days after their transplant. The dose will start at dose level 1 (2.0 x 106/kg). After each cohort of 3 patients has been treated at each of the dose levels, decisions will be made if the next high or lower dose level should be used. |
| Measure | Description | Time Frame |
|---|---|---|
| To assess toxicity by SAEs scored according to the adaptive CTCAE version 5 | Phase/safety/toxicity | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Evidence of immunity against specific viral pathogens- Ad, CMV and EBV in recipients of Multi-Virus CTLs | Immunity will be recorded. | 1 year |
| The incidence of Ad, EBV, and CMV systemic infections during the first 180 days post-transplant |
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Inclusion Criteria:
Patient age < 22 years.
Both genders and all races are eligible.
The patient population chosen for the T-cell depleted allogeneic HPCT from a related or unrelated allogeneic donor must meet eligibility based on institutional SOPs and/or the IRB approved T cell depleted allogeneic HPCT protocol which they are enrolled.
Must be willing to sign a written informed consent.
Patient Organ Status at the time of enrollment (pre-transplant)
Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months following CTL infusion. The male partner should use a condom.
Patients must be between 28 and 100 days post T-cell depleted allogeneic HPCT
Patients must meet the following criteria (within 72 hours of CTL infusion):
The Patient must not have the following conditions on the day of CTL infusion:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Julie-An Talano, MD | Medical College of Wisconsin/Children's Hospital of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
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Number of infections will be quantified.
| 1 year |
| ID | Term |
|---|---|
| D020031 | Epstein-Barr Virus Infections |
| D000257 | Adenoviridae Infections |
| D003586 | Cytomegalovirus Infections |
| ID | Term |
|---|---|
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
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