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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Primary Immune Deficiency Disorder, Cytomegalovirus Infections

Intervention / Treatment
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* Drug: viral specific cytotoxic t-lymphocytes


Participation Criteria
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Eligibility Criteria
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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 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. 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 CMV retinitis, meningitis, encephalitis, and/or cerebritis

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Refractory CMV<br>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<br>* 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.<br>* Other names: CMV CTLs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Patients will be monitored for adverse events following the administration of CMV CTLs | Patients will be followed for 12 weeks after each infusion | 
| Incidence of Response to Treatment | Patients will be followed for improvement in viral infection by monitoring CMV PCR weekly for response to treatment with CTLs | Patients will be followed 12 weeks after each infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMV, Cytomegalovirus, cytotoxic t-lymphocytes