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Patients with refractory ADV or CMV infection post allogeneic stem cell transplant will be randomized to either Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) plus standard of care (SOC) vs SOC alone.
We hypothesize that Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) manufactured by direct selection utilizing the CliniMACS Prodigy® and Cytokine Capture System® plus standard of care (SOC) vs SOC alone in children, adolescents and young adults (CAYA) following allogeneic hematopoietic stem cell transplantation (HSCT) with medically refractory viral infection/viremia and/or intolerant or resistant to anti-viral antibiotic therapy will be associated with a significantly improved probability of Day +100 (time of onset on study) viral progression free survival (VPFS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care Medication | Active Comparator | Patients will receive standard of care antiviral therapy for CMV or ADV at the discretion of the physician. |
|
| Standard of Care Medication plus Cytotoxic T-Lymphocytes (CTLs) | Experimental | Patients will be randomized to receiving standard of care antiviral therapy plus family matched donor derived CTLs. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard of Care Antiviral medications | Drug | Standard of Care medications will be selected by the treating physician for either ADV (Cohort 1) or CMV (cohort 2) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Viral PCR to determine resolution of disease | Patients will be monitored weekly by peripheral blood qtPCR values to monitor viral levels for resolution confirmation. | Day 100 |
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Patient Eligibility Cohort 1 (ADV) -Patients with ADV infections (Cohort 1) (pneumonitis, hepatitis, cystitis, and/or colitis) post AlloHSCT with one or more of the following: Increasing or persistent ADV RT-PCR DNA (> 1000 ADV PCR copies) after 7 days of appropriate anti-viral therapy AND/OR Medical intolerance to anti-viral therapies including one or more of the following: > grade 2 renal insufficiency secondary to cidofovir and/or other > grade 2 toxicities secondary to cidofovir AND/OR Known resistance to cidofovir
Patient Eligibility (Cohort 2) (CMV)
-Patients with CMV infections (pneumonitis, hepatitis, colitis) with one or more of the following: Increasing or persistent CMV RT-PCR DNA (>1000 copies) after 7 days of appropriate anti-viral therapy AND/OR Medical intolerance to anti-CMV antibiotic therapies: ANC > 500/mm3 secondary to ganciclovir AND/OR > grade 2 renal toxicity secondary to either foscarnet or cidofovir AND/OR Known resistance to ganciclovir and/or foscarnet
Donor Eligibility
Patient Exclusion Criteria (Both Cohorts)
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mitchell Cairo, MD | Contact | 914-594-2150 | mitchell_cairo@nymc.edu | |
| Lauren Harrison, RN | Contact | 617-285-7844 | lauren_harrison@nymc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Mitchell Cairo, MD | New York Medical College | Principal Investigator |
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This study is a prospective, open-label, randomized trial allocating patients to CTLs+SOC and SOC only at a 2:1 ratio. Patients will be enrolled to two cohorts, Cohort 1, ADV and Cohort 2, CMV. For patients with progressive viremia/disease (PD) in the SOC arm, crossover will be allowed to receive CTLs from an eligible family related donor that has screened positive to the specific viral PepTivator.
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| Viral CTLs | Biological | ADV or CMV family matched CTLs will be administered with SOC medications one every 2 weeks as needed up to 5 infusions |
|
| ID | Term |
|---|---|
| D000257 | Adenoviridae Infections |
| D003586 | Cytomegalovirus Infections |
| ID | Term |
|---|---|
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D006566 | Herpesviridae Infections |
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