Clinical trial NCT05664126: Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation
Official title: Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cytomegalovirus
Adenovirus
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2022-12-23
Enrollment: 42
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The investigators want to learn if CMV- and ADV-specific T-cells (cells that fight infections) isolated (selected) from a donor using an automated medical device can be a safe treatment for treating patients with CMV, and ADV after transplant.This study will test the effects and safety of giving VSTs produced here at St. Jude in treating the participant's infection.

Primary objective

To determine the efficacy of VSTs to achieve a ≥1 log10 reduction in CMV and/or ADV viral load in the peripheral blood 4 weeks after VST infusion.

When the initial viral load is \<1 log10 above the threshold of detection, the objective is to achieve a reduction to below the threshold of detection.

Secondary objectives

* Determine the safety of VSTs when used to treat CMV and/or ADV viremia post-HCT.
* Determine the proportion of patients who achieve a negative viral load at 3 months post-infusion.
* Assess the persistence of response for 6 months post-infusion.

Detailed description: The study will have 2 cohorts. Cohort A will include haploidentical donor who is identical to the stem cell donor. Cohort B will include haploidentical donor who is different from the stem cell donor. Seropositive donors will be screened for the presence of CMV- and ADV-specific T-cells using a functional flow cytometry assay. The donor will be considered suitable if the percentage of CD3+/IFN-γ+ cells is greater than 0.01% of CD3+ T-cells. Donor leukocytes will be collected using the Spectra Optia system. CMV- and ADV-specific T-cells will be isolated from donor leukocytes by 'IFN-γ-capture' technology using the Prodigy device over a 24-36 hour period and infused.

Eligibility criteria: Inclusion Criteria for Patients:

* Patients who have undergone haploidentical HCT or a matched-sibling/matched-unrelated donor HCT, and have CMV and/or ADV detected by PCR in the peripheral blood refractory to antiviral therapy per institutional BMTCT SOP 20.05.
* Definition of "refractory" viremia is persistent positive CMV or ADV viremia after 14 days of treatment per institutional SOP, or an increasing copy number (≥1 log) after 7 days of treatment.
* Patients have no suspected or confirmed GVHD.
* Availability of haploidentical donor for isolation of virus-specific T-cells.
* Have not received a Donor Lymphocyte Infusion in the past 4 weeks.
* Female patients of childbearing age must have a negative pregnancy test.
* Subject, parent, or guardian are capable of giving signed informed consent.
* Patients must have a shortening fraction \>26% or left ventricular ejection fraction \>40%.
* Patients must have a bilirubin less than or equal to 2.5mg/dL and alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal.
* Patients must have an estimated glomerular filtration rate (GFR) greater than 60mL/min/1.73m2.
* Patients must be free of severe infection which upon determination of the principal investigator precludes therapy with VST.
* Patients must have FVC \>50% predicted or if unable to perform pulmonary function testing must maintain pulse oximetry saturation \> 92% on room air.
* Patients must have engrafted with an ANC \>500 cells/mm3 for 3 consecutive days.

Inclusion criteria for donors

* Age ≥18 years.
* At least single haplotype matched (≥3/6) family member.
* Donor will be identical to the stem cell donor (Cohort A) or different from the stem cell donor (Cohort B).
* HIV negative.
* For females of childbearing age: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment AND not lactating with intent to breastfeed.
* Regarding donation eligibility, is identified as either having completed the process of donor eligibility determination as outlined in 21CFR 1271 and agency guidance or does not meet 21CFR 1271 eligibility requirements but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21CFR.
* Identified recipient with CMV and/or ADV reactivation post-HCT.

Exclusion Criteria for Patients:

* Active GVHD.
* Pregnancy.
* Inability to provide consent.
* Need for vasopressor or ventilatory support Patients receiving steroids \>0.5 mg/kg prednisone equivalent at the time of VST infusion
* Donor Lymphocyte Infusion within 4 weeks prior to VST infusion.
* Receipt of Thymoglobulin or Alemtuzumab within 30 days of VST infusion.
* Other concurrent infections (i.e. bacterial or fungal) that are not yet controlled on antimicrobial therapies.

Primary outcomes:
measure: Degree of reduction of CMV and/or ADV viral load
timeFrame: 4 weeks after VST infusion
Secondary outcomes:
measure: Incidence of infusion-related grade 3-5 adverse events 24 hours after infusion
timeFrame: 24 hours after infusion
measure: Incidence of AEs related to grade 3-4 cytokine release syndrome (CRS), or grade 1-2 CRS persist beyond 72 hours despite therapy
timeFrame: 4 weeks after VST infusion
measure: Incidence of Grade 3-4 Neurotoxicity of any duration
timeFrame: 4 weeks after VST infusion
measure: Incidence of Grade 3-4 GVHD
timeFrame: 4 weeks after VST infusion
measure: Incidence of grade 3-5 non hematologic toxicities attributable to VST
timeFrame: 4 weeks after VST infusion
measure: Incidence of secondary graft failure attributable to VST
timeFrame: 4 weeks after VST infusion
measure: Proportion of patients who achieve a negative viral load result at 3 months
timeFrame: 3 months after VST infusion
measure: Persistence of response at 6 months post-infusion
timeFrame: 6 months after VST infusion
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St . Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Naik Swati, MD
role: PRINCIPAL_INVESTIGATOR
References: