Back to results

Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation

Primary Purpose

Allogeneic Hematopoietic Stem Cell Transplantation

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

IFN-gamma-secreting HAdV antigen specific T cells

About this trial

This is an interventional supportive care trial for Allogeneic Hematopoietic Stem Cell Transplantation focused on measuring T Cell Therapy, Opportunistic Infection

Eligibility Criteria

3 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 who are 14 years and older must have the ability to understand and the willingness to sign a written informed consent document, or assent document.

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.

Sites / Locations

University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interferon (IFN)-gamma-secreting HAdV antigen specific T cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of patients with severe adverse events

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

Number of patients with viral response

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

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 from peripheral mononuclear cell collection to T cell product infusion

Full Information

NCT ID

NCT03378102

First Posted

December 15, 2017

Last Updated

January 26, 2023

Sponsor

Mari Dallas

1. Study Identification

Unique Protocol Identification Number

NCT03378102

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 Hematopoietic Stem Cell Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 4, 2019 (Actual)

Primary Completion Date

December 2028 (Anticipated)

Study Completion Date

December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mari Dallas

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

T Cell Therapy, Opportunistic Infection

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Interferon (IFN)-gamma-secreting HAdV antigen specific T cells

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

IFN-gamma-secreting HAdV antigen specific T cells

Other Intervention Name(s)

Antigen-selected, adenovirus-specific T Cells

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of patients with severe adverse events

Description

Time Frame

Up to 100 days after infusion

Secondary Outcome Measure Information:

Title

Number of patients with viral response

Description

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

Time Frame

Up to 30 days after infusion

Title

Number of patients with clinical response

Description

Time Frame

Up to 30 days after infusion

Title

Time from enrollment to T cell product infusion

Time Frame

Up to 24 hours

Title

Time from peripheral mononuclear cell collection to T cell product infusion

Time Frame

Up to 15 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Months

Accepts Healthy Volunteers

Eligibility 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 who are 14 years and older must have the ability to understand and the willingness to sign a written informed consent document, or assent document. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mari H Dallas, MD

Phone

216-844-0139

mhd27@case.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mari H Dallas, MD

Organizational Affiliation

University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mari H Dallas, MD

Phone

216-844-0139

mhd27@case.edu

First Name & Middle Initial & Last Name & Degree

Mari H Dallas, MD

12. IPD Sharing Statement

Learn more about this trial

Antigen Specific Adoptive T Cell Therapy for Adenovirus Infection After Hematopoietic Stem Cell Transplantation

We'll reach out to this number within 24 hrs