Back to resultsAdenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection
Primary Purpose
Adenovirus, Primary Immune Deficiency Disorder
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cytotoxic t-lymphocytes
Sponsored by
About this trial
This is an interventional treatment trial for Adenovirus focused on measuring adenovirus, primary immune deficiency disorder, cytotoxic t-lymphocytes
Eligibility Criteria
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 30.00 years
Females of childbearing potential with a negative urine pregnancy test
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.
- 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
-
Sites / Locations
- Children's Hospital Los AngelesRecruiting
- University of California San FranciscoRecruiting
- Children's Hospital of ColoradoRecruiting
- University of Colorado DenverRecruiting
- Johns Hopkins
- Washington UniversityRecruiting
- Nationwide Children's HosptialRecruiting
- Children's Hospital of PennsylvaniaRecruiting
- Medical College of Wisconsin/Children's Hospital of WisconsinRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
patients with adenoviral infection
Arm Description
patients will receive CTL dose x 1 with 2.5 × 10(4) CD3/kg for matched related donor and 0.5 × 104 CD3/kg for mis-matched related donor. Patients who don't respond to the first infusion may receive up to a total 5 CTL infusions.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Patients will be followed for adverse events following each infusion of ADV CTLs
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03266627
First Posted
August 25, 2017
Last Updated
October 24, 2023
Sponsor
New York Medical College
Collaborators
Children's Hospital of Philadelphia, Medical College of Wisconsin, Nationwide Children's Hospital, Johns Hopkins University, University of California, San Francisco, University of Colorado, Denver, Indiana University, Washington University School of Medicine, University of California, Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT03266627
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2018 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College
Collaborators
Children's Hospital of Philadelphia, Medical College of Wisconsin, Nationwide Children's Hospital, Johns Hopkins University, University of California, San Francisco, University of Colorado, Denver, Indiana University, Washington University School of Medicine, University of California, Los Angeles
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenovirus, Primary Immune Deficiency Disorder
Keywords
adenovirus, primary immune deficiency disorder, cytotoxic t-lymphocytes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
patients with adenoviral infection
Arm Type
Experimental
Arm Description
patients will receive CTL dose x 1 with 2.5 × 10(4) CD3/kg for matched related donor and 0.5 × 104 CD3/kg for mis-matched related donor. Patients who don't respond to the first infusion may receive up to a total 5 CTL infusions.
Intervention Type
Drug
Intervention Name(s)
cytotoxic t-lymphocytes
Other Intervention Name(s)
viral specific CTLs
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Patients will be followed for adverse events following each infusion of ADV CTLs
Time Frame
12 weeks after each infusion
Title
Incidence of Response to Treatment (Efficacy)
Description
Patients will be followed for improvement in viral infection by monitoring ADV PCR weekly for response to treatment with CTLs
Time Frame
12 weeks after last infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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.
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
-
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mitchell Cairo, MD
Phone
914-594-2150
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Lauren Harrison, RN
Phone
617-285-7844
Email
lauren_harrison@nymc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell Cairo, MD
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neena Kapoor, MD
Email
nkapoor@chla.usc.edu
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julia Chu, MD
Email
Julia.Chu2@ucsf.edu
Facility Name
Children's Hospital of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Verneris, MD
Phone
720-777-1234
Email
Michael.Verneris@childrenscolorado.org
First Name & Middle Initial & Last Name & Degree
Amanda Kinderman, MPH
Phone
303-724-3652
Email
amanda.kinderman@ucdenver.edu
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Verneris, MD
Email
MICHAEL.VERNERIS@CUANSCHUTZ.EDU
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenneth Cooke, MD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shalini Shenoy, MD
Email
shalinishenoy@wustl.edu
Facility Name
Nationwide Children's Hosptial
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dean Lee, MD, PhD
Phone
614-722-3550
Email
Dean.Lee@nationwidechildrens.org
Facility Name
Children's Hospital of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Bunin, MD
Phone
215-590-2255
Email
buninn@email.chop.edu
Facility Name
Medical College of Wisconsin/Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie A Talano, MD
Phone
414-955-4185
Email
jtalano@mcw.edu
First Name & Middle Initial & Last Name & Degree
Kathy Jodarski
Phone
414-266-2681
Email
kjodarski@chw.org
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection
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