Most Closely Human Leukocyte Antigen (HLA)-Matched CMV-specific T Lymphocytes (Viralym-C)

NCT02313857 | Completed Phase 1 DMC

• 1 other identifier: H35887 Viralym-C
• Study Type: interventional
• Target: 10
• 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. CMV can cause serious infections in patients with weak or suppressed immune systems. It usually affects the lungs, causing a very serious pneumonia, but it can also affect the gut, the liver and the eyes. Investigators want to see if they can use a kind of white blood cell called T cells to treat CMV infections that occur 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 CMV-specific T cells from the blood of healthy donors and created a bank of these cells. Investigators have previously successfully used frozen virus-specific T cell lines generated from healthy donors to treat virus infections after bone marrow transplant, and have now improved the production method and customized the bank of lines to specifically and exclusively target CMV. In this study, investigators want to find out if the banked CMV-specific T cells derived from healthy donors are safe and can help to treat CMV infection. The CMV-specific T cells (Viralym-C) are an investigational product not approved by the Food and Drug Administration (FDA).

Conditions

CMV Infections

Keywords

Viralym-C; Viral infections post HSCT; Virus-specific T cells

Outcome Measures

Primary Outcomes (1)

• Assessment of patients with adverse events after Viralym-C infusion

  To determine if administration of banked CMV-specific T cells (Viralym-C) derived from healthy donors are safe in patients with CMV infection after allogeneic stem cell transplant.

  42 days

Secondary Outcomes (2)

• Assessment of CMV load response to the Viralym-C infusion

  1 year

• Reconstitution of antiviral immunity after Viralym-C infusion

  3 months

Study Arms (1)

Viralym-C

EXPERIMENTAL

Partially HLA-matched Viralym-C cells will be thawed and given by intravenous injection. Patients will receive 2 x 10\^7 partially HLA-matched Viralym-C/m2 as a single infusion. If a patient has a partial response they are eligible to receive up to 4 additional doses at biweekly intervals. These doses would come from the original infused line if sufficient vials were available but may come from another line if there are insufficient cells in the original line.

Biological: Viralym-C

Interventions

Viralym-C BIOLOGICAL

Follow-up Assessments: The timing of follow-up visits is based on the date of Viralym-C infusion. If a patient has multiple Viralym-C infusions the schedule resets again at the beginning so follow up relates to the last Viralym-C infusion. Follow up will occur at 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 90 days, 180 days, and 365 days post enrollment.

Viralym-C

Eligibility Criteria

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

You may qualify if:

• 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 within 24 months.
• Persistent or recurrent cytomegalovirus infection or disease despite at least 7 days of standard therapy or failure of therapy as described below or if unable to tolerate standard therapy. Standard therapy is defined as antiviral therapy with ganciclovir or CMX001 (brincidofovir) as the agents of choice and foscarnet or cidofovir as second line agents.
• i.Cytomegalovirus infection: defined as the presence of CMV positivity as detected by Polymerase chain reaction (PCR) or pp65 antigenemia or culture from ONE site such as stool or blood or urine or nasopharynx.
• ii. Cytomegalovirus 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 broncheoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates or changes consistent with CMV retinitis on ophthalmologic examination.
• iii. 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 pp65 antigenemia after 7 days of antiviral therapy.
• Clinical status at enrollment to allow tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent).
• Hemoglobin (HgB)\>8.0 (may be transfused)
• Received transplant care locally and will remain in the Houston area for at least 6 weeks post Viralym-C infusion
• Pulse oximetry of \> 90% on room air
• Available Viralym-C T cell line
• Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

You may not qualify if:

• Patients receiving (anti-thymocyte globulin) ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of treatment with Viralym-C
• Patients with other uncontrolled/progressing infections defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. 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. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Patients who have received donor lymphocyte infusion (DLI) within 28 days of Viralym-C infusion.
• Patients who have received other investigational drugs within 28 days of Viralym-C infusion
• Patients with active acute Graft versus host disease (GVHD) grades II-IV.
• Active and uncontrolled relapse of malignancy

Sponsors & Collaborators

• AlloVir: lead

Study Sites (2)

Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital system

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P, Antin JH, Kapoor N, Pai SY, Rowley SD, Kebriaei P, Dey BR, Grilley BJ, Gee AP, Brenner MK, Rooney CM, Heslop HE. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013 Jun 27;121(26):5113-23. doi: 10.1182/blood-2013-02-486324. Epub 2013 Apr 22.

  PMID: 23610374 BACKGROUND

• Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, Leung K, Carrum G, Gee AP, Vera JF, Krance RA, Brenner MK, Rooney CM, Heslop HE, Leen AM. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014 Jun 25;6(242):242ra83. doi: 10.1126/scitranslmed.3008825.

  PMID: 24964991 BACKGROUND

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Bilal Omer, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Swati Naik, MD

  Texas Childrens Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 10, 2014
• Study Start: September 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: February 1, 2018
• Last Updated: December 26, 2018

Record last verified: 2018-12

Locations

US (2)