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Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03266627
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : July 20, 2020
Sponsor:
Collaborators:
Children's Hospital of Philadelphia
Medical College of Wisconsin
Nationwide Children's Hospital
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Brief Summary:

Related donor Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in children, adolescents and young adults with refractory ADV infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant.

Funding Source: FDA OOPD


Condition or disease Intervention/treatment Phase
Adenovirus Primary Immune Deficiency Disorder Drug: cytotoxic t-lymphocytes Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All eligible patients will receive one dose of CTLs at the same dose. Patients who meet the criteria may need additional CTL doses up to 5 total.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study in the Treatment of Refractory Adenovirus (ADV) Infection With Related Donor ADV Cytotoxic T-Lymphocytes (ADV-CTLs)in Children, Adolescents and Young Adult Recipients
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: patients with adenoviral infection
patients will receive CTL dose x 1 with 2.5 × 10(4) CD3/kg for matched related donor and 0.5 × 104 CD3/kg for mis-matched related donor. Patients who don't respond to the first infusion may receive up to a total 5 CTL infusions.
Drug: cytotoxic t-lymphocytes
adenovirus specific cytotoxic t-lymphocytes will be collected and manufactured from HLA matched related or HLA mis-matched related donors and administered to eligible patients with refractory adenovirus or PID.
Other Name: viral specific CTLs




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 12 weeks after each infusion ]
    Patients will be followed for adverse events following each infusion of ADV CTLs

  2. Incidence of Response to Treatment (Efficacy) [ Time Frame: 12 weeks after last infusion ]
    Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs



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Ages Eligible for Study:   1 Month to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  1. Patients with Adenovirus infections post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with:

    • Increasing or persistent quantitative ADV RT-PCR DNA copies despite two weeks of appropriate anti-viral therapy and/or
    • clinical symptoms attributed to adenovirus, including pneumonitis, hemorrhagic cystitis, colitis, hepatitis AND/OR
    • Medical intolerance to anti-viral therapies including:

      • grade 2 renal insufficiency secondary to cidofovir Consent: Written informed consent given (by patient or legal representative) prior to any study-related procedures.

    Performance Status > 30% (Lansky < 16 yrs and Karnofsky > 16 yrs) Age: 0.1 to 30.00 years

    Females of childbearing potential with a negative urine pregnancy test

  2. Donor Eligibility Related donor available with a T-cell response to the viral MACS® GMP PepTivator antigen(s) of adenovirus.

    a. Third Party Related Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with a T-cell response at least to the viral MACS® GMP PepTivator antigen(s) of adenovirus.

    AND Allogeneic donor disease screening is complete similar to hematopoietic stem cell donors (Appendix 1).

    AND Obtained informed consents by donor or donor legally authorized representative prior to donor collection.

  3. Patient exclusion criteria:

A patient meeting any of the following criteria is not eligible for the present study:

. Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of CTL infusion Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory adenovirus infection(s) Any medical condition which could compromise participation in the study according to the investigator's assessment Known HIV infection Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment.

Known hypersensitivity to iron dextran Patients unwilling or unable to comply with the protocol or unable to give informed consent.

Known human anti-mouse antibodies

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03266627


Contacts
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Contact: Mitchell Cairo, MD 914-594-2150 mitchell_cairo@nymc.edu
Contact: Lauren Harrison, RN 617-285-7844 lauren_harrison@nymc.edu

Locations
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United States, Colorado
Children's Hospital of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Michael Verneris, MD    720-777-1234    Michael.Verneris@childrenscolorado.org   
Contact: Amanda Kinderman, MPH    303-724-3652    amanda.kinderman@ucdenver.edu   
United States, Ohio
Nationwide Children's Hosptial Recruiting
Columbus, Ohio, United States, 43205
Contact: Dean Lee, MD, PhD    614-722-3550    Dean.Lee@nationwidechildrens.org   
United States, Pennsylvania
Children's Hospital of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Nancy Bunin, MD    215-590-2255    buninn@email.chop.edu   
United States, Wisconsin
Medical College of Wisconsin/Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Julie A Talano, MD    414-955-4185    jtalano@mcw.edu   
Contact: Kathy Jodarski    414-266-2681    kjodarski@chw.org   
Sponsors and Collaborators
New York Medical College
Children's Hospital of Philadelphia
Medical College of Wisconsin
Nationwide Children's Hospital
Investigators
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Principal Investigator: Mitchell Cairo, MD New York Medical College
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Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT03266627    
Other Study ID Numbers: NYMC 579
FD006363 ( Other Grant/Funding Number: FDA OOPD )
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mitchell Cairo, New York Medical College:
adenovirus
primary immune deficiency disorder
cytotoxic t-lymphocytes
Additional relevant MeSH terms:
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Adenoviridae Infections
Immunologic Deficiency Syndromes
DNA Virus Infections
Virus Diseases
Immune System Diseases