Clinical trial NCT03266627: Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Adenovirus
Primary Immune Deficiency Disorder
Keywords: adenovirus
primary immune deficiency disorder
cytotoxic t-lymphocytes
Lead sponsor: New York Medical College
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
name: Medical College of Wisconsin
name: Nationwide Children's Hospital
name: Johns Hopkins University
name: University of California, San Francisco
name: University of Colorado, Denver
name: Indiana University
name: Washington University School of Medicine
name: University of California, Los Angeles
First posted: 2017-08-30
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 79
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All eligible patients will receive one dose of CTLs at the same dose. Patients who meet the criteria may need additional CTL doses up to 5 total.
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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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Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 12 weeks after each infusion
measure: Incidence of Response to Treatment (Efficacy)
timeFrame: 12 weeks after last infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hosptial
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Pennsylvania
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: New York Medical College
name: Mitchell Cairo, MD
role: PRINCIPAL_INVESTIGATOR
References: