Status:
COMPLETED
Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)
Lead Sponsor:
Baylor College of Medicine
Collaborating Sponsors:
The Methodist Hospital Research Institute
Brigham and Women's Hospital
Conditions:
Adenovirus Infection
EBV Infection
Eligibility:
All Genders
Phase:
PHASE1
PHASE2
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 tha...
Detailed Description
Patients may be screened for study entry when they have persistent disease despite standard therapy as defined in the inclusion criteria. At that stage a search will be done of the available lines. Li...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- 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.
- EXCLUSION CRITERIA:
- 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
- Donors will be ineligible if they do not meet eligibility criteria for blood donors on the donor questionnaire or have positive infectious diseases testing on any of the tests outlined in the inclusion criteria.
Exclusion
Key Trial Info
Start Date :
November 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 1 2013
Estimated Enrollment :
50 Patients enrolled
Trial Details
Trial ID
NCT00711035
Start Date
November 1 2008
End Date
August 1 2013
Last Update
April 26 2016
Active Locations (8)
Enter a location and click search to find clinical trials sorted by distance.
1
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
2
University of Miami
Coral Gables, Florida, United States
3
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
4
Hackensack University
Bergen County, New Jersey, United States