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History of Changes for Study: NCT03378102
Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation
Latest version (submitted June 16, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 15, 2017 None (earliest Version on record)
2 January 29, 2018 Study Status
3 March 2, 2018 Study Status, Eligibility and Study Identification
4 August 3, 2018 Study Status
5 October 4, 2018 Study Status
6 October 18, 2018 Arms and Interventions and Study Status
7 January 2, 2019 Study Status
8 January 10, 2019 Recruitment Status, Study Status, Contacts/Locations and Oversight
9 January 10, 2020 Study Status
10 January 11, 2021 Sponsor/Collaborators and Study Status
11 March 9, 2022 Study Status
12 June 16, 2022 Study Status
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Study NCT03378102
Submitted Date:  December 15, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: CASE4Z17
Brief Title: Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation
Official Title: Antigen Specific Adoptive T Cell Therapy for Refractory Opportunistic Adenovirus Infection After a Related Donor Hematopoietic Stem Cell Transplantation
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2017
Overall Status: Not yet recruiting
Study Start: December 2017
Primary Completion: December 2019 [Anticipated]
Study Completion: December 2020 [Anticipated]
First Submitted: December 15, 2017
First Submitted that
Met QC Criteria:
December 15, 2017
First Posted: December 19, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
December 15, 2017
Last Update Posted: December 19, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Case Comprehensive Cancer Center
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

The purpose of this study is to determine if it is possible to treat an infection with a cell-based immunotherapy (therapy that uses the patient's own immune system to treat the infection). This treatment is called adoptive T cell therapy. Another purpose is to learn about the side effects and toxicities of adoptive T cell therapy.

Adoptive T cell therapy is an investigational (experimental) therapy that works by using the blood of a donor that has immunity against the virus. The donor cells are collected and then the cells, called T cells, that are capable of defending against the virus are selected out. These selected T cells are then infused back into the patient, to try to give the immune system the ability to fight the infection. Adoptive T cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).

Detailed Description:

Brief Background/Rationale: This study seeks to determine the feasibility of using antigen specific T cells isolated with the CliniMACS® Cytokine Capture System (CCS) for the treatment of adenovirus infections occurring after allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Primary Objective: To determine the feasibility of the treatment of opportunistic adenovirus infection after HSCT with adenovirus-specific, antigen-selected T cells, using the CliniMACS® Prodigy System.

Exploratory Objective(s)

  • To describe the safety profile of the infusion of virus - specific, antigen selected T cells.
  • To describe the toxicities related to infusion of virus - specific, antigen selected T cells.
  • To describe the rate of eradication of opportunistic adenovirus infection after treatment with virus-specific, antigen-selected T cells using the CliniMACS® Prodigy System.

Study Design:

This feasibility study will include a single treatment cohort including subjects who have failed to respond, are intolerant or have contraindications to antiviral agents used for treatment of Human Adenovirus (HAdV) (ganciclovir, valganciclovir, foscarnet and cidofovir).

Patients will be enrolled in a staggered pattern to ensure safety.

  • Patient 1 will be enrolled and observed for 30 days after infusion of virus specific T cells before enrollment of a subsequent patient.
  • Patient 2 will be enrolled ≥ 30 days after treatment of patient 1 and will be observed for 30 days before enrollment of a subsequent patient.
  • Subsequent patients will be enrolled in 6 cohorts of 3 subjects each. A safety period between cohorts of 30 days (between treatment of the last subject of one cohort and the first subject of the subsequent cohort).

Study Design: Staggered enrollment of patients with an observation period of 30 days after infusion. Safety monitoring points planned after patient No. 5 and No. 11

Open or close this module Conditions
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Keywords: T Cell Therapy
Opportunistic Infection
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Supportive Care
Study Phase: Early Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Interferon (IFN)-gamma-secreting HAdV antigen specific T cells
Virus-specific, antigen selected cells will be obtained using the CliniMACS® Prodigy System. the donor will be screened for their ability to produce an IFN-gamma- secretion response to HAdV by testing the donor's mononuclear cells with the Miltenyi Rapid Cytokine Inspector kit. Donors with appropriate IFN-gamma secretion response will undergo a steady state leukapheresis. The investigational product (IP) will be generated using the CCS-IFN enrichment program with an approximate duration time of 15 hours. After the IP passes release criteria, the IP will be suspended in 0.9 normal saline + 2.5% albumin and distributed for infusion. The IP will be infused within 4 hours as a bolus on day 0.
Biological: IFN-gamma-secreting HAdV antigen specific T cells
Antigen selected cells will be obtained using the CliniMACS(R) Prodigy System from a compatible donor. Isolated cells will be infused into the donor to treat human adenoviral infection after transplant
Other Names:
  • Antigen-selected, adenovirus-specific T Cells
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of patients with severe adverse events
[ Time Frame: Up to 100 days after infusion ]

This is a measure of feasibility: Severe adverse events are related to the infusion of virus-specific, antigen selected T cells, Grade ≥ 3 acute graft versus host disease,• Death within 30 days of the infusion of the virus-specific, antigen selected T cells that is considered by the investigators to be probably or possibly related to the T cell infusion
Secondary Outcome Measures:
1. Number of patients with viral response
[ Time Frame: Up to 30 days after infusion ]

Clearance: No measurable viral load after therapy Response: Decrease by ≥ 1 log after therapy Persistence: Change by < 1 log after therapy Progression: Increase by ≥1 log after therapy
2. Number of patients with clinical response
[ Time Frame: Up to 30 days after infusion ]

Clinical Response: Resolution of symptoms and signs of viral infection or reactivation Incomplete clinical response: Improvement, but not resolution of symptoms and signs of viral infection or reactivation Stable clinical disease: No change in symptoms or signs of viral infection Progressive clinical disease: Worsening of symptoms or signs of viral infection
3. Time from enrollment to T cell product infusion
[ Time Frame: Up to 24 hours ]

4. Time from peripheral mononuclear cell collection to T cell product infusion
[ Time Frame: Up to 15 hours ]

Open or close this module Eligibility
Minimum Age: 3 Months
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Patients must have received allogeneic HSCT and be greater than 30 days post-HSCT at the time of registration.
  • Patients must have evidence of documented HAdV infection/reactivation. Patients may be:
    • Symptomatic with any detectable viral load OR
    • Asymptomatic with viral load that is:

>1000 copies/ml in peripheral blood OR qualitative detection in stool, urine and/or other specimens

  • Patients must have poor response and/or contraindication to therapy:
    • Absence of an improvement of viral load (decrease by at least 1 log, i.e. 10-fold) after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir and/or foscarnet. OR
    • New, persistent and/or worsening HAdV-related symptoms, signs and/or markers of end organ compromise while on antiviral therapy with ganciclovir, valganciclovir or foscarnet. OR
    • Have contraindications or experience adverse effects of antiviral therapy with ganciclovir, valganciclovir, cidofovir or foscarnet.
  • Performance Score: Eastern Cooperative Oncology Group (ECOG) Performance Score ≤ 3. Karnofsky (≥ 16 years) or Lansky (<16 years) performance score ≥ 50
  • The effects of virus-specific, antigen-selected T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 4 weeks prior to study entry, for the duration of study participation and for 3 months after completing treatment.
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document, or assent document.

Donor selection priority: The original donor will be the first choice as source of T cells. If the original donor is unavailable for donation of peripheral mononuclear cells or does not meet all donor eligibility criteria, alternative related donors will be selected, with preference for those who have full Human Leukocyte Antigens (HLA) matching in 6/6 loci over those with partial HLA matching (≥ 3/6 HLA loci).

  • Related donor of T cells must be at least partially HLA compatible, matching with recipient in at least 3/6 HLA loci (HLA-A, HLA-B, and Human Leukosyte antigen antigen D Related Beta 1 (HLA-DRB1) loci will be considered for this).
  • Must have evidence of a serologic response (i.e. be seropositive) against HAdV.
  • Age ≥ 18 years
  • Must meet the criteria for donor selection defined in the Standard Operating Procedures (SOP) of University Hospitals Seidman Cancer Center Stem Cell Transplant Program (SOP B6.00 Allogeneic Donor Selection, Evaluation, and Management)
  • Must be capable of undergoing a single standard 2 blood volume leukapheresis or donation of one unit of whole blood

Exclusion Criteria:

  • Pregnant or breastfeeding women are excluded from this study. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with the agents described above, breastfeeding should be discontinued if the mother participates in this trial.
  • Patients with opportunistic viral infections other than HAdV.
  • Patients with active, grade II-IV, acute graft versus host disease (GVHD), chronic GVHD or any condition requiring high doses of glucocorticosteroid (>0.5 mg/kg/day prednisone or its equivalent) as treatment.
  • Treatment with antithymocyte globulin within 28 days of planned infusion of virus - specific, antigen selected T cells.
  • Treatment with virus - specific T cells within 6 weeks (42 days) of planned infusion.
Open or close this module Contacts/Locations
Central Contact Person: Mari H Dallas, MD
Telephone: 216-844-0139
Email: mhd27@case.edu
Study Officials: Mari H Dallas, MD
Principal Investigator
University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center
Locations: United States, Ohio
University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Contact:Contact: Mari H Dallas, MD 216-844-0139 mhd27@case.edu
Contact:Principal Investigator: Mari H Dallas, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
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Available IPD/Information:

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