Using genetically modified T-cells to treat viral infections in cancer patients

Study Assessing the Feasibility, Safety and Efficacy of Genetically Engineered Glucocorticoid Receptor Knock Out Virus Specific CTL Lines for Viral Infections in Immunosuppressed Cancer Patients

This study is testing whether specially modified immune cells can help cancer patients with weakened immune systems fight off serious viral infections.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT05101213 on ClinicalTrials.gov

What this trial studies

This phase I trial evaluates the feasibility and safety of administering genetically engineered cytotoxic T-lymphocytes (CTLs) to immunocompromised cancer patients suffering from viral infections such as adenovirus, BK virus, cytomegalovirus, JC virus, and COVID-19. The CTLs are specifically designed to target and eliminate these viruses, which are significant causes of morbidity and mortality in this patient population. Participants will receive the CTLs intravenously, with the possibility of additional infusions based on their response. The study will also monitor the persistence of these cells and assess overall survival and relapse-free survival over a follow-up period of 15 years.

Who should consider this trial

Good fit: Ideal candidates include immunocompromised cancer patients aged 18 and older with specific viral infections confirmed by PCR testing.

Not a fit: Patients without viral infections or those who have not undergone the required hematopoietic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel and effective treatment option for controlling viral infections in immunocompromised cancer patients.

How similar studies have performed: While the use of genetically modified T-cells is a novel approach, similar studies have shown promise in targeting viral infections in immunocompromised patients.

Eligibility criteria

Inclusion Criteria:

* Patients \> or = 18 years of age or older.
* For BKV, ADV or CMV infections: Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using bone marrow, peripheral blood stem cells or single or double umbilical cord blood. For JC virus and COVID19 infection: no prior hematopoietic stem cell transplantation (HSCT) is required.
* For BKV infection, patients need to have polymerase chain reaction (PCR) positive for BKV (in peripheral blood or urine) with consistent clinical symptoms.
* For ADV infection, patients need to have PCR positive for ADV in peripheral blood AND/OR patients need to fit criteria of probable or definitive adenovirus organ disease.
* For CMV infection, patients need to have PCR positive for CMV in peripheral blood AND/OR patients need to fit criteria of probable or definitive CMV disease.
* For JCV, patients need to have documented JC viral encephalitis or JC end-organ disease.
* For COVID-19 infection, patients need to have COVID-19 related pneumonia/acute respiratory distress syndrome (ARDS) to be enrolled, defined as patients with a positive COVID-19 test (bronchoalveolar lavage \[BAL\], nasal or pharyngeal) and radiological and clinical signs of pneumonia or ARDS.
* Written informed consent from patient or designated power of attorney.
* Subjects are also are required to consent to PA17-0483 for long term follow up per the guidelines set forth by the Food and Drug Administrations' (FDA's) Biologic Response Modifiers Advisory Committee (BRMAC).
* Negative pregnancy blood test in female patients of childbearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use at least two forms of birth control during the study and for at least 6 months after stopping treatment. Acceptable forms of birth control include intrauterine device (IUD), hormonal methods (birth control pills, injections, and implants), condoms, diaphragms, tubal ligation, or vasectomy.

Exclusion Criteria:

* Patients who have received anti-thymocyte globulin (ATG) within 14 days or have received donor lymphocyte infusion (DLI) or campath within 28 days of enrollment.
* Patients with other uncontrolled infections (excluding human immunodeficiency virus \[HIV\]/acquired immunodeficiency syndrome \[AIDS\]). For bacterial infections, patients must be receiving definitive therapy and have signs of improving infection prior to enrollment as determined by the principal investigator (PI). For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have signs of improving infection prior to enrollment as determined by the PI.
* Patients with active steroid refractory graft versus host disease (GVHD).
* Patients on immunosuppressive therapy other than tacrolimus, sirolimus or steroids
* Active and uncontrolled relapse of malignancy. Patients with controlled malignancy on maintenance therapy would be eligible for the study.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: May Daher, MD — M.D. Anderson Cancer Center
• Study coordinator: May Daher, MD

Conditions: Adenovirus Infection, BK Virus Infection, Cytomegaloviral Infection, Hematopoietic and Lymphoid Cell Neoplasm, JC Virus Infection, Malignant Solid Neoplasm, Symptomatic COVID-19 Infection Laboratory-Confirmed