Multivirus-specific T Cells for the Treatment of Virus Infections After Stem Cell Transplant

NCT02108522 | Completed Results DMC

• 1 other identifier: H-33903, CHARMS
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Infection

Keywords

CMV infection; EBV infection; HHV6 virus infection; BK virus infection; Adenovirus infection; JC virus infection; allogeneic stem cell transplant; Virus Specific T cells

Outcome Measures

Primary Outcomes (3)

• Number of Patients Where a Suitable VST Line Could be Found

  Consented subjects will be screened for a suitable VST line to asses feasibility of finding a sufficiently matching VST line.

  within 24 hours of receiving recipient HLA information

• Number of Patients With Acute GvHD Grades III-IV

  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.

  42 days

• Number of Patients With Grades 3-5 Non-hematologic Adverse Events Related to the T Cell Product

  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. Grade 4 Life-threatening consequences. Grade 5 Death related to AE.

  28 days

Secondary Outcomes (9)

• Number of Participants With a Viral Response at 42 Days

  42 days

• Number of Patients With Reconstitution of Antiviral Immunity (as Measured in Peripheral Blood)

  12 months

• Persistence of VSTs (in Peripheral Blood)

  Within 6 weeks

• Association Between High HLA Matching and Viral Outcomes

  6 weeks

• Association Between Low HLA Matching and Viral Outcomes

  6 weeks

Study Arms (1)

Multivirus Specific T cells

EXPERIMENTAL

Partially HLA-matched multivirus specific T cells (VSTs) will be thawed and given by intravenous injection. Patients will receive 2 x 10\^7 VSTs/m2 as a single infusion. In the rare case where insufficient banked cell product is available, a lower number of cells may be infused after discussion with the principal investigator, patient and/or guardian and the treatment team. If after the first treatment there is persistent infection, there is an option to receive more treatments. These additional treatments might be with cells from the same donor or another donor whose cells are also thought to be a good match for the patient and effective against their virus. This second product will be administered at the same dose level 28 days after the initial infusion, and subsequent infusions should be at least 14 days apart.

Biological: Multivirus Specific T cells

Interventions

Multivirus Specific T cells BIOLOGICAL

Multivirus Specific T cells

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For Initial VSTs and subsequent infusions: patients will be eligible following any type of allogeneic transplant if they have CMV, adenovirus, EBV, BK virus and/or HHV6 infection/disease persistent or recurrent despite 14 days of standard therapy OR after failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy. Patients with persistent JC virus infection will be eligible as well.
• Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells or single or double cord blood.
• Treatment of the following persistent or relapsed infections despite standard therapy;
• CMV: Treatment of persistent or relapsed CMV disease or infection after standard therapy. For CMV infection, standard therapy is defined as antiviral therapy with ganciclovir, foscarnet or cidofovir.
• CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates or changes consistent with CMV retinitis on ophthalmologic examination.
• CMV infection: defined as the presence of CMV positivity as detected by PCR or pp65 antigenemia or culture from ONE site such as stool or blood or urine or nasopharynx.
• Failure of antiviral therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR or pp65 antigenemia after 7 days of antiviral therapy.
• Adenovirus: Treatment of persistent adenovirus infection or disease despite standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function.
• Adenovirus infection: defined as the presence of adenoviral positivity as detected by PCR or culture from ONE site such as stool or blood or urine or nasopharynx.
• Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, DFA or culture from two or more sites such as stool or blood or urine or nasopharynx.
• Failure of therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR or any other quantitative assay) after 7 days of antiviral therapy.
• EBV: For treatment of persistent EBV infection despite standard therapy. For EBV infection, standard therapy is defined as rituximab given at 375mg/m2 in patients for 1-4 doses with a CD20+ve tumor.
• EBV infection: defined as Biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR,Or clinical or imaging findings consistent with EBV lymphoma and/or elevated EBV viral load in peripheral blood.
• Failure of therapy is defined as: Increase or less than 50% response at sites of disease for EBV lymphoma OR, Increase or a fall of less than 50% in EBV viral load in peripheral blood or any site of disease after 1st dose of rituximab.
• BK virus: Treatment of persistent BK virus infection or BK virus disease despite antiviral treatment with cidofovir or leflunomide. No clear standard treatment is defined. Cidofovir has been administered in low doses as well as high doses to HSCT patients with BK infections but no randomized trials are available proving its clinical efficacy. In small trials leflunomide had activity against BK virus, therefore we will consider this agent an acceptable alternative to cidofovir, given the absence of a clear first line option.

You may not qualify if:

• Patients receiving ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
• Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
• Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Patients who are less than 28 days removed from their allogeneic hematopoietic stem cell transplant or who have received donor lymphocyte infusions (DLI) within 28 days.
• Patients with active acute GVHD grades II-IV.
• Active and uncontrolled relapse of malignancy

Sponsors & Collaborators

• AlloVir: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.

  PMID: 7581076 BACKGROUND

• Pfeiffer T, Tzannou I, Wu M, Ramos C, Sasa G, Martinez C, Lulla P, Krance RA, Scherer L, Ruderfer D, Naik S, Bocchini C, Fraser IP, Patel B, Ward D, Wang T, Heslop HE, Leen AM, Omer B. Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting. Clin Cancer Res. 2023 Jan 17;29(2):324-330. doi: 10.1158/1078-0432.CCR-22-2415.

  PMID: 36628536 DERIVED

MeSH Terms

Conditions

Infections; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections

Limitations and Caveats

Limited information is available regarding patients who were screened for the study but were not administered investigational product. Data are preliminary and unaudited.

Results Point of Contact

• Title: Iain Fraser, MD
• Organization: AlloVir

ClinicalTrials@allovir.com

833-409-2281

Study Officials

• Bilal Omer, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2014
• First Posted: April 9, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: July 20, 2021
• Results First Posted: July 19, 2021

Record last verified: 2021-07

Locations

US (2)