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

Cytomegalovirus Infections Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03266640
• Other study ID #: NYMC 580
• Secondary ID: FD006363
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: New York Medical College
• Contact: Mitchell S Cairo, MD
• Phone: 914-594-2150
• Email: mitchell_cairo[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Immunologic Deficiency Syndromes
• Infections
• Primary Immune Deficiency Disorder
• Primary Immunodeficiency Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	Nationwide Children's Hosptial	Columbus	Ohio
United States	Indiana University	Indianapolis	Indiana
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Medical College of Wisconsin/Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	New York Medical College	Valhalla	New York

Sponsors (9)

Lead Sponsor	Collaborator
New York Medical College	Children's Hospital Los Angeles, Children's Hospital of Philadelphia, Indiana University, Johns Hopkins University, Medical College of Wisconsin, Nationwide Children's Hospital, University of California, San Francisco, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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