Donor Virus-Specific CMV or AdV CTL to Treat CMV or AdV Reactivation or Disease After Solid Organ or HCT

NCT03665675 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-17199NCI-2018-01412
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This trial studies the side effects and how well allogeneic cytomegalovirus-specific cytotoxic T lymphocytes (donor cytomegalovirus \[CMV\] specific cytotoxic T-lymphocytes \[CTLs\]) or allogeneic adenovirus-specific cytotoxic T lymphocytes (donor adenovirus-specific \[AdV\] specific CTLs) work in treating CMV or AdV reactivation or infection in participants who have undergone stem cell transplant or solid organ transplant. White blood cells from donors may be able to kill cancer cells in patients with cytomegalovirus or adenovirus that has come back after a stem cell or solid organ transplant.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation Recipient; Cytomegalovirus; Donor; Solid Organ Transplantation Recipient; Adenovirus

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0

  Measured as the proportion of patients with acute (a) graft versus host disease (GvHD) grades III-IV or graft rejection/failure within 30 days of the last dose of cytotoxic T-lymphocytes (CTLs) or grades 3-5 infusion-related adverse events within 7 days of the last does of CTLs or grades 4-5 non-hematological adverse events within 30 days of the last dose of CTLs and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities. Will be calculated by dividing by all evaluable patients and the corresponding 95% confidence intervals will be calculated.

  Up to 30 days post infusion

• Feasibility defined as identifying a suitable donor within 4 weeks and meeting minimum T cell doses in the final product

  Up to 1 year

Secondary Outcomes (10)

• Antiviral activity defined as response to viral load

  At day 28

• Persistence of infused CTLs as measured by T cell gene rearrangement and effects on clinical signs of viral infection

  Up to 1 year

• Overall survival

  From last CTL infusion till death, assessed at 6 and 12 months

• Risk for chronic GVHD

  At 6 and 12 months post CTL infusion

• Systemic infections

  Within 6 months of CTL infusion

Study Arms (2)

Treatment (CMV-specific CTLs)

EXPERIMENTAL

Participants receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes IV. Participants with persistent infection are eligible for second infusion after 28 days.

Biological: Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes

Treatment (AdV-specific CTLs)

EXPERIMENTAL

Patients receive allogeneic adenovirus-specific cytotoxic T Lymphocytes IV. Participants with persistent infection are eligible for second infusion after 28 days.

Biological: Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes

Interventions

Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes BIOLOGICAL

Given intravenously

Treatment (CMV-specific CTLs)

Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes BIOLOGICAL

Given intravenously

Treatment (AdV-specific CTLs)

Eligibility Criteria

• Age: 1 Year - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have solid organ transplant or have received allogeneic hematopoietic stem cell transplant.
• Cohort A (CMV): Must have documented CMV disease or reactivation, as by:
• Viremia as detected by quantitative polymerase chain reaction (PCR) (\> 500 IU/ml) in the peripheral blood requiring treatment OR
• High risk for antiviral failure due to history of recurrent CMV reactivations or evidence of antiviral drug resistance, OR
• Unable to tolerate antiviral drugs due to renal toxicity, bone marrow suppression, transfusion dependent anemia and thrombocytopenia or neutropenia requiring growth factor support or other related organ injury
• Cohort B (AdV): Must have documented AdV infection or reactivation, as by:
• Symptomatic subject with any detectable viral load in blood, OR
• Symptomatic subject with qualitative AdV detection in compartment of current symptomatology, including stool, urine, and/or other specimens (bronchoalveolar lavage (BAL), nasal swab, CSF, etc.), irrespective of blood viral load, OR
• New, persistent, and/or worsening AdV-related symptoms, signs, and/or markers of end organ compromise while receiving antiviral therapy (ie cidofovir), OR
• Asymptomatic with a viral load \> 1000 copies/ml in peripheral blood, OR
• Unable to tolerate antiviral treatment due to renal toxicity, bone marrow suppression, transfusion dependent anemia and thrombocytopenia or neutropenia requiring growth factor support or other related organ injury
• Karnofsky (age \> 16 years) or Lansky performance score \> 70 (age \< 16)
• Available seropositive haploidentical or matched donor who is without evidence of infection that would otherwise preclude donation
• Negative pregnancy test in female patients if applicable (childbearing potential, has not received a full-intensity conditioning regimen
• Written informed consent and/or signed assent line from patient, parent or guardian

You may not qualify if:

• Receipt of anti-thymocyte globulin (ATG), alemtuzumab, or other T-cell depleting agents within 21 days of screening for enrollment.
• Receipt of \> 0.5mg/kg/day of prednisone or steroid equivalent at the time of enrollment. Stable GVHD is permitted as long as patients are on stable dose steroids of less than or equal to 0.5 mg/kg/day of prednisone or steroid equivalent.
• Evidence of uncontrolled infection as follows:
• Bacterial infections - patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment.
• Fungal infections - patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
• Patients with hemodynamic instability attributable to bacterial sepsis or new symptoms, worsening physical signs or radiographic findings attributable to concomitant bacterial or fungal infection are excluded. Patients who require ventilator support for CMV pneumonitis are not excluded. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Receipt of donor lymphocyte infusion (DLI) within 28 days.
• Patients with active acute graft versus host disease (GvHD) grades II-IV requiring \> 0.5 mg/kg/day of prednisone or steroid equivalent or T-cell depleting immunosuppression.
• Acute graft rejection in solid organ transplantation requiring augmented immunosuppression with T-cell depleting agents or steroids as mentioned above.
• Active and uncontrolled relapse of malignancy.

Sponsors & Collaborators

• Sumithira Vasu: lead

Study Sites (2)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

SUSPENDED

Related Links

• The Jamesline

MeSH Terms

Conditions

Adenoviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Sumithira Vasu, MBBS

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Nicole Szuminski

CONTACT

614-688-9796; Nicole.Szuminski@osumc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: September 11, 2018
• Study Start: November 7, 2020
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): December 20, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)