Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03378102|
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : June 21, 2022
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).
|Condition or disease||Intervention/treatment||Phase|
|Allogeneic Hematopoietic Stem Cell Transplantation||Biological: IFN-gamma-secreting HAdV antigen specific T cells||Early Phase 1|
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.
- 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.
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||Antigen Specific Adoptive T Cell Therapy for Refractory Opportunistic Adenovirus Infection After a Hematopoietic Stem Cell Transplantation|
|Actual Study Start Date :||January 4, 2019|
|Estimated Primary Completion Date :||August 2022|
|Estimated Study Completion Date :||October 2022|
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. IP will be suspended in 0.9 normal saline + 2.5% albumin and distributed for infusion and infused within 4 hours as a bolus on day 0.
Subjects will receive virus-specific, antigen selected T cells within a targeted range of 1 x 10^3- 2 x 10^5 per kg of recipient weight.
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 Name: Antigen-selected, adenovirus-specific T Cells
- 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
- 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
- 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
- Time from enrollment to T cell product infusion [ Time Frame: Up to 24 hours ]
- Time from peripheral mononuclear cell collection to T cell product infusion [ Time Frame: Up to 15 hours ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03378102
|Contact: Mari H Dallas, MDemail@example.com|
|United States, Ohio|
|University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Mari H Dallas, MD 216-844-0139 firstname.lastname@example.org|
|Principal Investigator: Mari H Dallas, MD|
|Principal Investigator:||Mari H Dallas, MD||University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center|