Most Closely Human Leukocyte Antigen (HLA)-Matched BK Virus-specific T Lymphocytes (Viralym-B)

NCT02313844 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: H35885 Viralym-B
• Study Type: interventional
• Target: N/A
• 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. BK virus (BKV) is a virus that can cause serious life-threatening infections in patients who have weak immune systems. It affects the urinary tract, and can cause frequent urination, blood in the urine, and severe pain. Investigators want to see if they can use a kind of white blood cell called T cells to treat BKV 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 BKV-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 BKV. In this study, investigators want to find out if the banked BKV-specific T cells derived from healthy donors are safe and can help to treat BK virus infection. The BKV-specific T cells (Viralym-B) are an investigational product not approved by the Food and Drug Administration (FDA).

Conditions

BK Virus Infection

Keywords

BK virus; Virus specific T cells; Viral infections

Outcome Measures

Primary Outcomes (1)

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

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

  42 days

Secondary Outcomes (2)

• Assessment of BK viral load response to the Viralym-B infusion

  1 year

• Reconstitution of antiviral immunity after Viralym-B infusion

  3 months

Study Arms (1)

Viralym-B

EXPERIMENTAL

Partially HLA-matched Viralym-B cells will be thawed and given by intravenous injection. Patients will receive 2 x 10\^7 partially HLA-matched Viralym-B/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-B

Interventions

Viralym-B BIOLOGICAL

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

Viralym-B

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 BK virus 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 cidofovir or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function.
• i. BK virus infection: defined as the presence of BK virus positivity as detected by Polymerase chain reaction (PCR) or culture in one site such as blood or urine.
• ii. BK virus disease: defined as presence of BK virus detectable by culture or PCR in blood or urine or other body fluids and symptoms of disease including but not limited to persistent microscopic and macroscopic hematuria or detectable BK virus in more than one site.
• 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 any other quantitative assay) 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 B infusion
• Pulse oximetry of \> 90% on room air
• Available Viralym-B 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-B
• 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-B infusion.
• Patients who have received other investigational drugs within 28 days of Viralym-B 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

Virus Diseases

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Swati Naik, MD

  Texas Childrens Hospital

  PRINCIPAL INVESTIGATOR

• Bilal Omer, MD

  The Methodist Hospital Research Institute

  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: March 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 9, 2018

Record last verified: 2018-04

Locations

US (2)