Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection

Primary Immune Deficiency Disorder Clinical Trial

Official title:

A Pilot Study in the Treatment of Refractory Adenovirus (ADV) Infection With Related Donor ADV Cytotoxic T-Lymphocytes (ADV-CTLs)in Children, Adolescents and Young Adult Recipients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03266627
• Other study ID #: NYMC 579
• 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 Cairo, MD
• Phone: 914-594-2150
• Email: mitchell_cairo[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Related donor Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in children, adolescents and young adults with refractory ADV 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 Adenovirus infections post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with:

• Increasing or persistent quantitative ADV RT-PCR DNA copies despite two weeks of appropriate anti-viral therapy and/or

• clinical symptoms attributed to adenovirus, including pneumonitis, hemorrhagic cystitis, colitis, hepatitis AND/OR

• Medical intolerance to anti-viral therapies including:

• grade 2 renal insufficiency secondary to cidofovir 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 years

Females of childbearing potential with a negative urine pregnancy test

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

a. Third Party Related Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with a T-cell response at least to the viral MACS® GMP PepTivator antigen(s) of adenovirus.

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 CTL infusion Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients =16 years) score =30% Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory adenovirus infection(s) 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

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Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus
• Immunologic Deficiency Syndromes
• Primary Immune Deficiency Disorder
• Primary Immunodeficiency Diseases

Intervention

Drug:
• cytotoxic t-lymphocytes
adenovirus specific cytotoxic t-lymphocytes will be collected and manufactured from HLA matched related or HLA mis-matched related donors and administered to eligible patients with refractory adenovirus or PID.

Locations

Country	Name	City	State
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	University of Colorado Denver	Aurora	Colorado
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

Sponsors (10)

Lead Sponsor	Collaborator
New York Medical College	Children's Hospital of Philadelphia, Indiana University, Johns Hopkins University, Medical College of Wisconsin, Nationwide Children's Hospital, University of California, Los Angeles, University of California, San Francisco, University of Colorado, Denver, 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 followed for adverse events following each infusion of ADV CTLs	12 weeks after each infusion
Primary	Incidence of Response to Treatment (Efficacy)	Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs	12 weeks after last infusion