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Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)

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: NCT03266640
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : September 28, 2022
Sponsor:
Collaborators:
Children's Hospital of Philadelphia
Medical College of Wisconsin
Nationwide Children's Hospital
Johns Hopkins University
University of California, San Francisco
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Study Description
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Brief Summary:

CMV cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered in children, adolescents and young adults (CAYA) with refractory cytomegalovirus (CMV) 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
Cytomegalovirus Infections Primary Immune Deficiency Disorder Drug: viral specific cytotoxic t-lymphocytes Phase 2

Study Design
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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 be given CMV specific CTLs and dose is based on donor source: HLA matched and HLA mismatced
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study in the Treatment of Refractory Cytomegalovirus (CMV) Infections With Related Donor CMV Specific Cytotoxic T-cells (CTLs) in Children, Adolescents and Young Adult Recipients
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Refractory CMV
Patients with refractory CMV will be given one dose of CMV specific CTLs. HLA matched donors will get Dose 2.5 × 10(4) CD3/kg recipient weight; HLA mismatched will get 0.5x10(4) CD3/kg recipient weight. Additional doses may be given for a total of 5 doses if patients do not have a response to the first dose with a reduction in viral load to normal limits.
 Drug: viral specific cytotoxic t-lymphocytes
CMV specific CTLs will be collected from HLA matched or mismatched donors and manufactured in a GMP facility and administered to patients with refractory CMV infection.
Other Name: CMV CTLs


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

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


Eligibility Criteria
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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 refractory CMV infection post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with either

  • Increasing or persistent quantitative qRT-PCR DNA copies despite two weeks of appropriate anti-viral therapy AND/OR
  • Medical intolerance to anti-viral therapies including:

  • ANC < 500/mm2 secondary to ganciclovir

    • 2 renal toxicity with foscarnet And/or
  • known resistance to ganciclovir and/or foscarnet

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 30.99 years Females of childbearing potential with a negative urine pregnancy test

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

a. Third Party Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party related allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with IgG positive to CMV and/or a T-cell response to the CMV MACS® GMP PepTivator .

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 CMV CTL infusion Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of CMV CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CMV CTL infusion Thymoglobulin (ATG), Alemtuzumab or T cell immunosuppressive monoclonal antibodies within 30 days Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% CMV retinitis Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory CMV infection.

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

Contacts and Locations
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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): NCT03266640


Contacts
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Contact: Mitchell S Cairo, MD 914-594-2150 mitchell_cairo@nymc.edu
Contact: Lauren Harrison, RN 6172857844 lauren_harrison@nymc.edu

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Neena Kapoor, MD       nkapoor@chla.usc.edu   
University of California San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Julia Chu, MD       Julia.Chu2@ucsf.edu   
United States, Maryland
Johns Hopkins Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Kenneth Cooke, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Shalini Shenoy, MD       shalinishenoy@wustl.edu   
United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell S Cairo, MD    914-594-2150    mitchell_cairo@nymc.edu   
Principal Investigator: Mitchell S. Cairo, MD         
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
Johns Hopkins University
University of California, San Francisco
Investigators
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Principal Investigator: Mitchell S Cairo, MD New York Medical College
More Information
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Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT03266640    
Other Study ID Numbers: NYMC 580
FD006363 ( Other Grant/Funding Number: FDA OOPD )
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: September 28, 2022
Last Verified: September 2022
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:
Cytomegalovirus
CMV
cytotoxic t-lymphocytes
Additional relevant MeSH terms:
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Infections
Cytomegalovirus Infections
Primary Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Herpesviridae Infections
 DNA Virus Infections
Virus Diseases
Immune System Diseases
Genetic Diseases, Inborn