NCT02108522: CHARMS

Administration of Most Closely HLA-matched Multivirus-specific Cytotoxic T-Lymphocytes for the Treatment of EBV, CMV, Adenovirus, HHV6, and BK Virus Infections Post Allogeneic Stem Cell Transplant

Completed NA Results posted Last updated 16 July 2021

What this trial tests

NA trial testing Multivirus Specific T cells in Infection in 82 participants. Completed in 1 December 2019.

Timeline

1 June 2014

Primary endpoint
1 December 2018

1 December 2019

Quick facts

Lead sponsor	AlloVir
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	82
Start date	1 June 2014
Primary completion	1 December 2018
Estimated completion	1 December 2019
Sites	2 locations across United States

Drugs / interventions tested

• Multivirus Specific T cells — full drug profile →

Conditions studied

• Infection — all drugs for Infection →

Sponsor

AlloVir — full company profile →

Who can join

Eligibility, any sex, with Infection. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of Patients Where a Suitable VST Line Could be Found
  Time frame: within 24 hours of receiving recipient HLA information
  Consented subjects will be screened for a suitable VST line to asses feasibility of finding a sufficiently matching VST line.
• Number of Patients With Acute GvHD Grades III-IV
  Time frame: 42 days
  Safety of VSTs based on patients with acute GvHD grades III-IV within 42 days of the last dose of VSTs. Acute GVHD grading was performed by the consensus conference criteria (1). Grade 0 represents no acute GvHD. Grade 4 represents the most severe acute GvHD.
• Number of Patients With Grades 3-5 Non-hematologic Adverse Events Related to the T Cell Product
  Time frame: 28 days
  Safety of VSTs based on patients with grades 3-5 non-hematologic adverse events that are at least possibly related to the T cell product within 28 days of the last VST dose by NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe or medically significant but not immediately life-threatening.

Sponsor's own description

Patients enrolled on this study will have received a stem cell transplant. After a transplant, while the immune system grows back the patient is at risk for infection. Some viruses can stay in the body for life and if the immune system is weakened, like after a transplant, they can cause life threatening infections.

Patients enrolled on this study will have had an infection with one or more of the following viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV), BK virus, JC virus, adenovirus or HHV6 (Human Herpes Virus 6).

Investigators want to see if they can use a kind of white blood cell called T cells to treat infections of these viruses after a transplant. Investigators have observed in other studies that treatment with specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical when a patient already has an infection.

Investigators have now generated multivirus-specific T cells (VSTs) from the blood of healthy donors and created a bank of these cells. Investigators have previously successfully used frozen multivirus-specific T cells from healthy donors to treat virus infections after bone marrow transplant and now have improved the production method to make it safer and target more viruses.

In this study, investigators want to find out if they can use these banked VSTs to fight infections caused by the viruses mentioned above.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.
   Tzannou I, Papadopoulou A, Naik S, Leung K, et al · · 2017 · cited 350× · PMID 28783452 · DOI 10.1200/jco.2017.73.0655
2. The Evolution of T-cell Therapies for Solid Malignancies.
   Fousek K, Ahmed N. · · 2015 · cited 66× · PMID 26240290 · DOI 10.1158/1078-0432.ccr-14-2675
3. Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting.
   Pfeiffer T, Tzannou I, Wu M, Ramos C, et al · · 2023 · cited 62× · PMID 36628536 · DOI 10.1158/1078-0432.ccr-22-2415
4. Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer.
   Ragoonanan D, Khazal SJ, Abdel-Azim H, McCall D, et al · · 2021 · cited 39× · PMID 33608690 · DOI 10.1038/s41571-021-00474-4
5. Virus-Specific T Cells: Broadening Applicability.
   Barrett AJ, Prockop S, Bollard CM. · · 2018 · cited 37× · PMID 29032062 · DOI 10.1016/j.bbmt.2017.10.004
6. CMV Prevention and Treatment in Transplantation: What's New in 2019.
   Stern A, Papanicolaou GA. · · 2019 · cited 23× · PMID 31732823 · DOI 10.1007/s11908-019-0699-0
7. Adoptive Immunotherapy for Prophylaxis and Treatment of Cytomegalovirus Infection.
   Ouellette CP. · · 2022 · cited 17× · PMID 36366468 · DOI 10.3390/v14112370
8. Adoptive T cell therapy for the treatment of viral infections.
   Arasaratnam RJ, Leen AM. · · 2015 · cited 10× · PMID 26605324 · DOI 10.3978/j.issn.2305-5839.2015.10.12