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

This study has been completed.
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Brigham and Women's Hospital
Massachusetts General Hospital
M.D. Anderson Cancer Center
National Marrow Donor Program
The EMMES Corporation
Duke University
Beth Israel Deaconess Medical Center
Children's Hospital Los Angeles
Children's Hospital Boston
University of Miami
Hackensack University Medical Center
University of California, Los Angeles
Information provided by (Responsible Party):
Helen Heslop, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00711035
First received: June 20, 2008
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Adenovirus Infection
EBV Infection
Biological: Trivirus Specific CTLs
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation Or Infection With Adenovirus, CMV and EBV After Hemopoietic Stem Cell Transplantation (HSCT)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • 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 107 CHM-CTLs/m2. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: November 2008
Study Completion Date: August 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trivirus Specific CTLs
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

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.


  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  1. 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.
  2. CMV, adenovirus or EBV infection persistent despite standard therapy

    1. 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
    2. 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
    3. 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)
  3. 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.
  4. Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone.
  5. Written informed consent from patient, parent or guardian.
  6. 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:

  1. Patients receiving ATG, or Campath or other immunosuppressive monoclonal antibodies within 28 days of screening for enrollment.
  2. 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.

  3. Patients who have received donor lymphocyte infusion (DLI) within 28 days.
  4. Patients with active acute GVHD grades II-IV.
  5. 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711035

Locations
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
United States, Florida
University of Miami
Coral Gables, Florida, United States
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New Jersey
Hackensack University
Bergen County, New Jersey, United States
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Houston Methodist Hospital
Houston, Texas, United States, 77073
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Brigham and Women's Hospital
Massachusetts General Hospital
M.D. Anderson Cancer Center
National Marrow Donor Program
The EMMES Corporation
Duke University
Beth Israel Deaconess Medical Center
Children's Hospital Los Angeles
Children's Hospital Boston
University of Miami
Hackensack University Medical Center
University of California, Los Angeles
Investigators
Principal Investigator: Helen Heslop, MD Baylor College of Medicine
  More Information

No publications provided by Baylor College of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Helen Heslop, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00711035     History of Changes
Other Study ID Numbers: 22994-CHALLAH, CHALLAH, U54HL081007
Study First Received: June 20, 2008
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
CMV
Adenovirus
EBV
non-myeloablative transplants
Prior allogeneic hematopoietic stem cell transplant

Additional relevant MeSH terms:
Adenoviridae Infections
Epstein-Barr Virus Infections
DNA Virus Infections
Virus Diseases
Herpesviridae Infections
Tumor Virus Infections
Neoplasms, Experimental
Neoplasms

ClinicalTrials.gov processed this record on July 24, 2014