R-MVST Cells for Viral Infections

Overseen By Prakash Satwani, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must not be taking: Corticosteroids, Antimetabolites, Checkpoint inhibitors, others

Disqualifiers: Uncontrolled infections, GVHD, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

18 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like corticosteroids at high doses, specific immunosuppressants, and investigational products must not have been taken recently. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment R-MVST Cells for viral infections?

Research on similar cell therapies, like invariant natural killer T (iNKT) cells, shows they have strong antiviral properties and can help regulate the immune system, which suggests that R-MVST Cells might also be effective in treating viral infections. ^{1 2 3 4 5}

Is R-MVST cell therapy safe for humans?

While specific safety data for R-MVST cells is not available, similar therapies using engineered natural killer T cells have been shown to be safe in clinical trials for cancer, with no severe adverse events reported. These therapies have been well-tolerated in patients, suggesting a favorable safety profile. ^{6 7 8 9 10}

How is the R-MVST Cells treatment different from other treatments for viral infections?

R-MVST Cells treatment is unique because it involves using specially modified cells to target viral infections, which may offer a more targeted approach compared to traditional antiviral drugs. This method could potentially provide a novel way to treat viral infections by harnessing the body's own immune cells. ^{11 12 13 14 15}

What is the purpose of this trial?

The primary objective is to determine the safety and feasibility of administering R-MVST cells to patients with refractory viral reactivation and/or symptomatic disease caused by Epstein Barr Virus (EBV), cytomegalovirus (CMV), adenovirus (ADV) or BK virus. R-MVST cells will be generated on-demand from the closest partially human leukocyte antigen (HLA)-matched (minimum haploidentical) healthy donors or from the original allo-transplant donor if available. The investigator will closely monitor the recipients for potential toxicities including graft-versus-host disease (GVHD) post-infusion. Secondary objectives are to determine the effect of R-MVST infusion on viral load, possible recovery of antiviral immunity post-infusion and for evidence of clinical responses and overall survival. Recipients will be monitored for secondary graft failure at day 28 post R-MVST infusion.

Research Team

Prakash Satwani, MD

Principal Investigator

Professor of Pediatrics

Eligibility Criteria

This trial is for children and young adults with stubborn viral infections like CMV, EBV, ADV, or BK virus. Participants must have a matching healthy donor available for T-cell donation. They should not have conditions that could worsen with the treatment.

Inclusion Criteria

I have a history of transplant and my body is fighting a virus infection poorly despite treatment.

I am between 3 months and 25 years old.

I've had multiple or recurrent viral infections after a stem cell transplant.

Exclusion Criteria

I haven't taken methotrexate or similar drugs in the last week.

I am taking steroids equivalent to or more than 0.5mg/kg of prednisone.

Patients who have received investigational (IND) product within 14 days of infusion of the R-MVST cells

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive R-MVST cell infusions to treat viral infections

Up to 28 days

Multiple visits for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of GVHD and other toxicities

Up to 1 year

Regular follow-up visits

Treatment Details

Interventions

• R-MVST Cells

Trial Overview The study tests R-MVST cells to treat persistent viral infections. These special immune cells are made quickly from donors who partially match the patient's tissue type and are monitored for safety and effectiveness against the viruses.

Participant Groups

Group I: Group C: Other Immunocompromised Patients Experimental Treatment 1 Intervention

Patients who have infection due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or BK virus, and are immunocompromised for reasons other than hematopoietic stem cell transplant or solid organ transplant.

Group II: Group B: Solid Organ Transplant Recipients Experimental Treatment 1 Intervention

Patients who have infection due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or BK virus, and are recipients of solid organ transplant.

Group III: Group A: Allogenic Stem Cell Transplant Recipients Experimental Treatment 1 Intervention

Patients who have infection due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or BK virus, and are recipients of hematopoietic stem cell transplant.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Findings from Research

The administration of autologous invariant natural killer T (iNKT) cells in 10 patients with advanced hepatocellular carcinoma was found to be safe and well-tolerated, with no severe adverse events reported, even at high doses (up to 1×10^10 cells).

Expanded iNKT cells showed a strong T-helper 1-like immune response, producing significant amounts of cytokines associated with antitumor activity, suggesting potential effectiveness in treating hepatocellular carcinoma, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial. Gao, Y., Guo, J., Bao, X., et al.[2021]

In a phase 1 trial involving three children with relapsed or resistant neuroblastoma, engineered NKT cells showed promising safety, with no dose-limiting toxicities observed after infusion, despite some hematologic adverse events linked to pre-treatment conditioning.

One patient experienced a significant anti-tumor response, with regression of bone metastatic lesions, indicating that CAR-NKT cells can effectively target tumors and expand in the body after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis. Heczey, A., Courtney, AN., Montalbano, A., et al.[2023]

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Distinct and overlapping effector functions of expanded human CD4+, CD8α+ and CD4-CD8α- invariant natural killer T cells. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

On the use of donor-derived iNKT cells for adoptive immunotherapy to prevent leukemia recurrence in pediatric recipients of HLA haploidentical HSCT for hematological malignancies. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Improved V&#948;2+ T cells recovery correlates to reduced incidences of mortality and relapse in acute myeloid leukemia after hematopoietic transplantation. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Off-the-Shelf CAR-NK Cells for Cancer Immunotherapy. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Isolation and development of a reticuloendotheliosis virus-transformed lymphoblastoid cell line from chicken spleen cells. [2021]

12. France pubmed.ncbi.nlm.nih.gov

Some biological properties of herpesvirus saimiri from chronically infected monolayer and suspension cultures. [2014]

13. United States pubmed.ncbi.nlm.nih.gov

In vitro myelosuppressive effects of the parvovirus minute virus of mice (MVMi) on hematopoietic stem and committed progenitor cells. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Cell-type-specific gene delivery into neuronal cells in vitro and in vivo. [2019]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Acquisition of susceptibility to vesicular stomatitis virus infection by murine resident peritoneal cells during culturing in vitro. [2008]