Back to results

T Cell Therapy of Opportunistic Cytomegalovirus Infection

Primary Purpose

Cytomegalovirus Infections, Hematopoietic Stem Cell Transplant, Opportunistic Infections

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

CMV specific adoptive t-cells

About this trial

This is an interventional supportive care trial for Cytomegalovirus Infections focused on measuring Immunotherapy, T-Cell Therapy, Lymphoproliferative Disorder

Eligibility Criteria

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

Inclusion Criteria:

Patients must have received allogeneic hematopoietic stem cell transplant and be greater than 30 days post-transplant at the time of registration
Patients must have documented opportunistic CMV infection, or reactivation; the criteria include (both of the following criteria must be met)
- Patients may have asymptomatic viremia (>1000 copies/ml) OR presence of symptoms secondary to CMV infection, AND
- Patients must have ONE OF THE NEXT FOUR CRITERIA:
  - Absence of an improvement of viral load after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold) or
  - New, persistent and/or worsening CMV-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 or foscarnet.
  - Second recurrence of CMV viremia, CMV-related symptoms, signs and/or markers of end organ compromise.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
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.

Exclusion Criteria:

Pregnant or breastfeeding women are excluded from this study.
Patients with opportunistic viral infections other than CMV.
Patients with active, grade 2-4, acute graft vs. 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.

Donor eligibility

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 HLA-DRB1 loci will be considered for this).
Must have evidence of a serologic response (i.e. be seropositive) against CMV.
Age ≥ 18 years
Must meet the criteria for donor selection defined in the Standard Operating Procedures of University Hospitals Seidman Cancer Center Stem Cell Transplant Program
Must be capable of undergoing a single standard 2 blood volume leukapheresis or donation of one unit of whole blood

Sites / Locations

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CMV specific adoptive t-cells

Arm Description

This study involves a one-time infusion of the experimental CMV specific adoptive t-cells. After this infusion, patients will be followed for 4 weeks.

Outcomes

Primary Outcome Measures

Incidence of adverse events

To determine the feasibility of the intervention, the study will record the incidence of adverse events, including graft versus host disease and other complications will be evaluated using binomial distribution theory and their 95% confidence intervals (CIs) will be also estimated using Wilson's method

Secondary Outcome Measures

Eradication rate of opportunistic CMV infections

The eradication rate will be the disappearance of opportunistic CMV infections with the use of CMV-specific, antigen-selected T cells using the CliniMACS Prodigy System over the total number CMV infections.

response rate

A response rate of 25% is considered unacceptable; and the anticipated response rate is approximately 55% for the study population using the cell therapy.

Full Information

NCT ID

NCT02982902

First Posted

December 2, 2016

Last Updated

September 28, 2023

Sponsor

Mari Dallas

1. Study Identification

Unique Protocol Identification Number

NCT02982902

Brief Title

T Cell Therapy of Opportunistic Cytomegalovirus Infection

Official Title

Antigen Specific Adoptive T Cell Therapy for Opportunistic Cytomegalovirus Infection Occurring After Stem Cell Transplant

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 27, 2020 (Actual)

Primary Completion Date

March 2024 (Anticipated)

Study Completion Date

March 2025 (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

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine if a specific type of cell-based immunotherapy, using T-cells from a donor that are specific against cytomegalovirus (CMV) is feasible to treat infections by CMV. Adoptive T-cell therapy is an investigational (experimental) therapy that works by using the blood of a donor and selecting the T-cells that can respond against a specific infectious entity. These selected T-cells are then infused to 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

The primary objective of this study is to determine the feasibility of the treatment of opportunistic cytomegalovirus (CMV) infections after hematopoietic stem cell transplant (HSCT) with virus-specific, antigen-selected T-cells, selected using the CliniMACS prodigy system. Secondary Objective(s) To describe the safety profile of the infusion of CMV- specific, antigen selected T-cells. To describe the toxicities related to infusion of CMV- specific, antigen selected T-cells. To describe the rate of eradication of opportunistic CMV infections after HSCT and and treatment with CMV-specific, antigen-selected T-cells using the CliniMACS Prodigy System. This feasibility study will include a single treatment cohort.

6. Conditions and Keywords

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

Cytomegalovirus Infections, Hematopoietic Stem Cell Transplant, Opportunistic Infections

Keywords

Immunotherapy, T-Cell Therapy, Lymphoproliferative Disorder

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

CMV specific adoptive t-cells

Arm Type

Experimental

Arm Description

This study involves a one-time infusion of the experimental CMV specific adoptive t-cells. After this infusion, patients will be followed for 4 weeks.

Intervention Type

Biological

Intervention Name(s)

CMV specific adoptive t-cells

Other Intervention Name(s)

immunotherapy

Intervention Description

It is expected that the cell dose will be in the range of 10^3 - 10^5 virus - specific, antigen selected T cells per kg of recipient weight.

Primary Outcome Measure Information:

Title

Incidence of adverse events

Description

Time Frame

Up to 100 days after transplant

Secondary Outcome Measure Information:

Title

Eradication rate of opportunistic CMV infections

Description

Time Frame

Up to 100 days after transplant

Title

response rate

Description

A response rate of 25% is considered unacceptable; and the anticipated response rate is approximately 55% for the study population using the cell therapy.

Time Frame

Up to 100 days after transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have received allogeneic hematopoietic stem cell transplant and be greater than 30 days post-transplant at the time of registration Patients must have documented opportunistic CMV infection, or reactivation; the criteria include (both of the following criteria must be met) Patients may have asymptomatic viremia (>1000 copies/ml) OR presence of symptoms secondary to CMV infection, AND Patients must have ONE OF THE NEXT FOUR CRITERIA: Absence of an improvement of viral load after ≥ 14 days of antiviral therapy with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log, i.e. 10-fold) or New, persistent and/or worsening CMV-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 or foscarnet. Second recurrence of CMV viremia, CMV-related symptoms, signs and/or markers of end organ compromise. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 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. Exclusion Criteria: Pregnant or breastfeeding women are excluded from this study. Patients with opportunistic viral infections other than CMV. Patients with active, grade 2-4, acute graft vs. 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. Donor eligibility 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 HLA-DRB1 loci will be considered for this). Must have evidence of a serologic response (i.e. be seropositive) against CMV. Age ≥ 18 years Must meet the criteria for donor selection defined in the Standard Operating Procedures of University Hospitals Seidman Cancer Center Stem Cell Transplant Program Must be capable of undergoing a single standard 2 blood volume leukapheresis or donation of one unit of whole blood

Central Contact Person:

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

Mari H Dallas, MD

Phone

1-800-641-2422

CTUReferral@UHhospitals.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mari H Dallas, MD

Organizational Affiliation

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106-5065

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mari H Dallas, MD

Phone

800-641-2422

CTUReferral@UHhospitals.org

First Name & Middle Initial & Last Name & Degree

Mari H Dallas, MD

12. IPD Sharing Statement

Learn more about this trial

T Cell Therapy of Opportunistic Cytomegalovirus Infection

We'll reach out to this number within 24 hrs