Clinical trial NCT03266640: Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cytomegalovirus Infections
Primary Immune Deficiency Disorder
Keywords: Cytomegalovirus
CMV
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: Washington University School of Medicine
name: Indiana University
name: Children's Hospital 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 be given CMV specific CTLs and dose is based on donor source: HLA matched and HLA mismatced
Primary purpose: TREATMENT

Brief 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 criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Patients will be followed for 12 weeks after each infusion
measure: Incidence of Response to Treatment
timeFrame: Patients will be followed 12 weeks after each 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: 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: Valhalla
country: United States
facility: New York Medical College
state: New York
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 S Cairo, MD
role: PRINCIPAL_INVESTIGATOR
References: