search
Back to results

Donor T Cell Therapy in Treating Immunocompromised Patients With Adenovirus-Related Disease

Primary Purpose

Hematopoietic and Lymphoid Cell Neoplasm, Immunocompromised

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic and Lymphoid Cell Neoplasm

Eligibility Criteria

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

Inclusion Criteria:

  • Immunocompromised patients with any hematological malignancies.
  • Written informed consent and/or signed assent from patient, parent or guardian.
  • Negative pregnancy test in female patients of childbearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
  • Asymptomatic adenovirus viremia defined as no symptoms of adenovirus disease and EITHER two positive and quantifiable quantitative polymerase chain reaction (qPCR) tests taken one week apart or one single measurement with >= 1000 copies.
  • Patients with criteria of probable or definitive adenoviral diseases.

Exclusion Criteria:

  • Patients receiving prednisone > 0.1 mg/kg/day or equivalent at time of enrollment, or who have received anti-thymocyte globulin (ATG) within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment.
  • Patients with other uncontrolled infections: For bacterial infections, patients must be receiving therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Active acute graft versus host disease (GVHD) grade >= 2.

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (allogeneic adenovirus-specific CTLs)

Arm Description

Within two weeks of enrollment, patients receive allogeneic adenovirus-specific CTLs IV over 30 minutes. Patients may receive additional allogeneic adenovirus-specific CTL infusions at the discretion of the investigator in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0
Safety and tolerability will be assessed by laboratory assessments, adverse events, and serious adverse events. Adverse events will be graded by the CTCAE version 4.0. Categorical measures will be summarized using frequencies and percentages while continuous variables will be summarized using means, standard deviations, medians, minimums, and maximums.
Assessment of response to allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs)
The proportion of patients experiencing response will be computed with associated 95% confidence interval (CI). The 95% exact CI for the feasibility criterion of 50% will extend from 25% to 75% for 16 patients.

Secondary Outcome Measures

Overall survival (OS)
OS will be defined from treatment start date to date of death. Patients who are still alive at end of study will be censored. OS will be estimated using the Kaplan-Meier method.
Relapse-free survival (RFS)
RFS (original malignancy) will be defined from treatment start date to the date of documented disease recurrence or death. Patients who are still alive without disease progression at end of study will be censored. RFS will be estimated using the Kaplan-Meier method.
Cumulative incidence of adenovirus reactivation after therapy
Cumulative incidence of adenovirus reactivation after therapy will be assessed using the competing risks method. The competing risks will include relapse and death and patients who are still alive without disease progression at end of study will be censored.
Cumulative incidence of graft versus host disease (GVHD)
Cumulative incidence of grade 2-4 GVHD, grade 3-4 GVHD, and chronic GVHD will be assessed using the competing risks method. The competing risks will include relapse and death and patients who are still alive without disease progression at end of study will be censored.
Reconstitution of anti-adenovirus immunity
The number of adenovirus specific T-cells in blood will be determined for each patient. The proportion of patients with population of cells that are specific and can be detected will be computed along with associated 95% CI.

Full Information

First Posted
January 29, 2018
Last Updated
August 17, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT03425526
Brief Title
Donor T Cell Therapy in Treating Immunocompromised Patients With Adenovirus-Related Disease
Official Title
Administration of Off-the-Shelf, Expanded, Most Closely HLA Matched, Third Party Adenovirus Specific T Cells for Therapy of Adenovirus Related Disease in Immunocompromised Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2018 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I trial studies the side effects of allogeneic adenovirus-specific cytotoxic T lymphocytes (donor T cell therapy) and to see how well they work in treating patients with a weakened immune system (immunocompromised) and adenovirus-related disease. Allogeneic adenovirus-specific cytotoxic T lymphocytes are made from donated blood cells grown in the laboratory and are designed to kill viruses that can cause infections in immunocompromised patients with adenovirus-related disease.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched adenovirus specific T cell lines generated by ex vivo expansion as therapy of asymptomatic adenovirus viremia or adenovirus-related disease in immunocompromised hosts. SECONDARY OBJECTIVES: I. To obtain preliminary data about the efficacy of administering most closely HLA-matched adenovirus specific T cell lines generated by ex vivo expansion as therapy of adenovirus viremia or adenovirus-related disease. II. To assess the persistence of the administered cells in the patients. OUTLINE: Within two weeks of enrollment, patients receive allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs) intravenously (IV) over 30 minutes. Patients may receive additional allogeneic adenovirus-specific CTL infusions at the discretion of the investigator in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic and Lymphoid Cell Neoplasm, Immunocompromised

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (allogeneic adenovirus-specific CTLs)
Arm Type
Experimental
Arm Description
Within two weeks of enrollment, patients receive allogeneic adenovirus-specific CTLs IV over 30 minutes. Patients may receive additional allogeneic adenovirus-specific CTL infusions at the discretion of the investigator in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes
Other Intervention Name(s)
Allogeneic Adenovirus-specific CTLs
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0
Description
Safety and tolerability will be assessed by laboratory assessments, adverse events, and serious adverse events. Adverse events will be graded by the CTCAE version 4.0. Categorical measures will be summarized using frequencies and percentages while continuous variables will be summarized using means, standard deviations, medians, minimums, and maximums.
Time Frame
Up to 1 year
Title
Assessment of response to allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs)
Description
The proportion of patients experiencing response will be computed with associated 95% confidence interval (CI). The 95% exact CI for the feasibility criterion of 50% will extend from 25% to 75% for 16 patients.
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
OS will be defined from treatment start date to date of death. Patients who are still alive at end of study will be censored. OS will be estimated using the Kaplan-Meier method.
Time Frame
From the start of study treatment up to 1 year
Title
Relapse-free survival (RFS)
Description
RFS (original malignancy) will be defined from treatment start date to the date of documented disease recurrence or death. Patients who are still alive without disease progression at end of study will be censored. RFS will be estimated using the Kaplan-Meier method.
Time Frame
From the start of study treatment up to 1 year
Title
Cumulative incidence of adenovirus reactivation after therapy
Description
Cumulative incidence of adenovirus reactivation after therapy will be assessed using the competing risks method. The competing risks will include relapse and death and patients who are still alive without disease progression at end of study will be censored.
Time Frame
Up to 1 year
Title
Cumulative incidence of graft versus host disease (GVHD)
Description
Cumulative incidence of grade 2-4 GVHD, grade 3-4 GVHD, and chronic GVHD will be assessed using the competing risks method. The competing risks will include relapse and death and patients who are still alive without disease progression at end of study will be censored.
Time Frame
Up to 1 year
Title
Reconstitution of anti-adenovirus immunity
Description
The number of adenovirus specific T-cells in blood will be determined for each patient. The proportion of patients with population of cells that are specific and can be detected will be computed along with associated 95% CI.
Time Frame
Up to 1 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Immunocompromised patients with any hematological malignancies. Written informed consent and/or signed assent from patient, parent or guardian. Negative pregnancy test in female patients of childbearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study. Asymptomatic adenovirus viremia defined as no symptoms of adenovirus disease and EITHER two positive and quantifiable quantitative polymerase chain reaction (qPCR) tests taken one week apart or one single measurement with >= 1000 copies. Patients with criteria of probable or definitive adenoviral diseases. Exclusion Criteria: Patients receiving prednisone > 0.1 mg/kg/day or equivalent at time of enrollment, or who have received anti-thymocyte globulin (ATG) within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment. Patients with other uncontrolled infections: For bacterial infections, patients must be receiving therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. Active acute graft versus host disease (GVHD) grade >= 2.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Marin, MD
Phone
713-792-8750
Email
dmarin@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Marin
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Marin
Phone
713-792-8750
First Name & Middle Initial & Last Name & Degree
David Marin

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

Donor T Cell Therapy in Treating Immunocompromised Patients With Adenovirus-Related Disease

We'll reach out to this number within 24 hrs