Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)

NCT00711035 | Completed Phase 1 DMC

• 3 other identifiers: 22994-CHALLAHCHALLAHU54HL081007
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

This trial is designed to evaluate the feasibility, safety and efficacy of most closely HLA-matched multivirus specific CTL lines (CHM-CTLs) in HSCT patients with EBV, CMV or adenovirus infections that are persistent despite standard therapy. The primary objective of the study is to assess safety and feasibility of administering CTLs. Survival data will be collected by asking the transplant center to submit the routine Transplant Essential Data form that is sent to the Stem Cell Transplant Outcomes Database at 100 days and 1 year and includes data on survival status and other outcome measures.

Conditions

Adenovirus Infection; EBV Infection

Keywords

CMV; Adenovirus; EBV; non-myeloablative transplants; Prior allogeneic hematopoietic stem cell transplant

Outcome Measures

Primary Outcomes (1)

• The primary purpose of the study is to assess the safety of administering CHM-CTLs in transplant patients with EBV, CMV, or adenovirus infection. We have elected to use a dose of 2 x 10^7 CHM-CTLs/m2.

  1 year

Study Arms (1)

Trivirus Specific CTLs for EBV, CMV and Adenovirus Infection

EXPERIMENTAL

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: Trivirus Specific CTLs for EBV, CMV and Adenovirus Infection

Interventions

Trivirus Specific CTLs for EBV, CMV and Adenovirus Infection BIOLOGICAL

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

Trivirus Specific CTLs for EBV, CMV and Adenovirus Infection

Eligibility Criteria

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

You may qualify if:

• Pts will be eligible following any type of allogeneic transplant if they have CMV, adenovirus or EBV infection persistent to standard therapy (as defined below).
• Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or single or double cord blood within 18 months.
• CMV, adenovirus or EBV infection persistent despite standard therapy
• For CMV infection: i.Pts with 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 ii. Failure of antiviral therapy: defined as the continued presence of pp65 antigenemia (\>1+ cell/100,000 cells) or DNAemia (as defined by reference lab performing PCR assay but usually \>400 copies/ml) after at least 7 days of antiviral therapy OR iii. Relapse after antiviral therapy defined as recurrence of either pp65 antigenemia or DNAemia after at least 2 weeks of antiviral therapy iv. For CMV infection, standard therapy is defined as 7 days therapy with Ganciclovir, Foscarnet or Cidofovir for patients with disease or recurrence after 14 days therapy
• For EBV infection: i. EBV infection is defined as: 1. Biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR OR 2. Or clinical or imaging findings consistent with EBV lymphoma and elevated EBV viral load in peripheral blood. ii. For EBV infection, standard therapy is defined as rituximab given at 375mg/m\^2 in patients for 1-4 doses with a CD20+ve tumor iii. Failure is defined as: 1. There was an increase or less than 50% response at sites of disease for EBV lymphoma OR 2. There was a rise or a fall of less than 50% in EBV viral load in peripheral blood or any site of disease
• For adenovirus infection or disease: i. Adenovirus infection is defined as the presence of adenoviral positivity as detected by PCR, DAA or culture from ONE site such as stool, blood, urine, or nasopharynx OR ii. Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from two or more sites such as stool or blood or urine or nasopharynx iii. Standard therapy is defined as 7 days therapy with Cidofovir (if renal function permits this agent to be given) iv. Failure is 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)
• Pts with multiple CMV, EBV or Adenovirus infections are eligible given that each infection is persistent despite standard therapy as defined above. Patients with multiple infections with one persistent infection and one controlled infection are eligible to enroll.
• Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone.
• Written informed consent from patient, parent or guardian.
• Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
• The informed consent process will begin at recognition of subject eligibility and consent will be obtained per institutional practices before study therapy is initiated. Subjects will initially sign a screening consent to enable a search to be made for a line. If a line is available they will sign the treatment consent.
• Up to 4 additional doses can be administered if a partial response is obtained and patient meets eligibility criteria for subsequent infusions. The minimum interval between subsequent infusions is 2 weeks.
• Donors will be eligible if they meet eligibility criteria for blood donors on history and exam by a transplant donor physician and have negative infectious diseases testing.

You may not qualify if:

• For initial CTL and subsequent infusions:
• Patients receiving ATG, or Campath or other immunosuppressive 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 have received donor lymphocyte infusion (DLI) within 28 days.
• Patients with active acute GVHD grades II-IV.
• Active and uncontrolled relapse of malignancy

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• M.D. Anderson Cancer Center: collaborator
• National Marrow Donor Program: collaborator
• The Emmes Company, LLC: collaborator
• Duke University: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Children's Hospital Los Angeles: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Boston Children's Hospital: collaborator
• University of Miami: collaborator
• Hackensack Meridian Health: collaborator
• University of California, Los Angeles: collaborator

Study Sites (8)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of Miami

Coral Gables, Florida, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Hackensack University

Bergen County, New Jersey, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77073, United States

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Adenoviridae Infections; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Helen Heslop, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: July 8, 2008
• Study Start: November 1, 2008
• Primary Completion: October 1, 2012
• Study Completion: August 1, 2013
• Last Updated: April 26, 2016

Record last verified: 2016-03

Locations

US (8)