Using donor T-cells to treat viral infections after stem cell transplantation

Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

This study is testing if special immune cells from related donors can help patients who had a stem cell transplant fight off viral infections like CMV and ADV.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: N/A to 18 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: Alemtuzumab, prednisone
• Locations: 1 site (Memphis, Tennessee)
• Trial ID: NCT05664126 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of virus-specific T-cells (VSTs) derived from haploidentical donors for treating Cytomegalovirus (CMV) and Adenovirus (ADV) infections in patients who have undergone hematopoietic cell transplantation (HCT). The study will involve two cohorts, one with donors identical to the stem cell donor and another with different haploidentical donors. Participants will receive an infusion of these isolated T-cells, and the primary objective is to achieve a significant reduction in viral load within four weeks. Secondary objectives include assessing safety, the proportion of patients achieving negative viral loads, and the persistence of the treatment response over six months.

Who should consider this trial

Good fit: Ideal candidates include patients who have undergone haploidentical or matched donor HCT and have refractory CMV or ADV infections.

Not a fit: Patients with suspected or confirmed graft-versus-host disease (GVHD) or those who have received a donor lymphocyte infusion in the past four weeks may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel and effective option for patients suffering from persistent viral infections after transplantation.

How similar studies have performed: While the approach of using virus-specific T-cells is promising, it is still considered a novel method with limited prior success in similar studies.

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 (may use estimated GFR that is auto calculated in the EHR).
* 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 able to maintain pulse oximetry saturation \> 92% on room air.
* Gut diarrhea \<1 liter/day (adults) or \<20mL/kg/day (children) or if unable to quantify, then occurrence of 4 stools per day above baseline.
* 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 severe uncontrolled concurrent infections (i.e. bacterial or fungal) that are not yet controlled on antimicrobial therapies.

Where this trial is running

Memphis, Tennessee

• St . Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Naik Swati, MD — St. Jude Children's Research Hospital
• Study coordinator: Naik Swati, MD

Conditions Cytomegalovirus; Adenovirus