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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. Identifier: NCT03266640
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : December 3, 2018
Children's Hospital of Philadelphia
Medical College of Wisconsin
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

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) or with primary immunodeficiencies (PID).

Condition or disease Intervention/treatment Phase
Cytomegalovirus Infections Primary Immune Deficiency Disorder Drug: viral specific cytotoxic t-lymphocytes Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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 : December 31, 2020
Estimated Study Completion Date : December 31, 2021

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

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

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

1. Patients with refractory CMV infection post allogeneic HSCT or with primary immunodeficiencies 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 The first 3 patients entered and possibly the next 3 patients entered will be limited to age 12.0 - 30.99 years. See section 9.3.4 for age eligibility in the first 6 patients.

There will be a temporary hold until 45 days after the 3rd patient and possibly the 6th patient has received their CMV-CTLs, The study should be reopened for patients of all ages (0.1-30.99 years). (See Section 9.3.4 for instructions) 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).

  1. Original allogeneic donor if available, IgG positive for CMV and confirmatory testing to respond to MACS GMP Peptivator CMV pp65.
  2. 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

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 identifier (NCT number): NCT03266640

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Contact: Mitchell S Cairo, MD 914-594-2150
Contact: Lauren Harrison, RN 6172857844

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United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell S Cairo, MD    914-594-2150   
Principal Investigator: Mitchell S. Cairo, MD         
United States, Pennsylvania
Children's Hospital of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Nancy Bunin, MD    215-590-2255   
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   
Contact: Kathy Jodarski    414-266-2681   
Sponsors and Collaborators
New York Medical College
Children's Hospital of Philadelphia
Medical College of Wisconsin
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Principal Investigator: Mitchell S Cairo, MD New York Medical College

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Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College Identifier: NCT03266640     History of Changes
Other Study ID Numbers: NYMC 580
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
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:
cytotoxic t-lymphocytes

Additional relevant MeSH terms:
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Cytomegalovirus Infections
Immunologic Deficiency Syndromes
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Immune System Diseases