RecruitingPhase 2NCT03266640

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

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

Sponsor

New York Medical College

Enrollment

20 participants

Start Date

Nov 1, 2018

Study Type

INTERVENTIONAL

Conditions

Cytomegalovirus Infections Primary Immune Deficiency Disorder

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

Eligibility

Min Age: 1 MonthMax Age: 79 Years

Inclusion Criteria12

\. 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
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 79.99 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.

Exclusion Criteria5

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 CMV retinitis, meningitis, encephalitis, and/or cerebritis

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Interventions

DRUGviral 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.