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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03665675
Other study ID # OSU-17199
Secondary ID NCI-2018-01412
Status Recruiting
Phase Early Phase 1
First received
Last updated
Start date November 7, 2020
Est. completion date December 31, 2024

Study information

Verified date March 2024
Source Ohio State University Comprehensive Cancer Center
Contact The Ohio State University Comprehensive Cancer Center
Phone 800-293-5066
Email OSUCCCClinicaltrials@osumc.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

PRIMARY OBJECTIVE I. Assess the safety and feasibility of administering virus specific-CTLs from haploidentical donors in transplant patients both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) with CMV/AdV infection despite standard therapy. OUTLINE:Patients are assigned to 1 of 2 Cohorts. COHORT A: Patients receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes intravenously (IV). Patients undergo blood, urine, saliva, cerebrospinal fluid (CSF), and bronchoalveolar fluid sample collection on the trial. COHORT B: Patients receive allogeneic adenovirus-specific cytotoxic T Lymphocytes IV. Patients undergo blood, urine, saliva, CSF, and bronchoalveolar fluid sample collection on the trial. After completion of study treatment, participants are followed up at 1 year.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date December 31, 2024
Est. primary completion date December 31, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 1 Year to 85 Years
Eligibility Inclusion Criteria: - 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 - DONOR - Human leukocyte antigen (HLA)-haploidentical or full-match to the patient as determined by institutional standards - Cohort A: CMV seropositive, defined as detection of serum CMV immunoglobulin G (IgG) - Cohort B: AdV seropositive, defined as detection of serum AdV IgG - Age 18 or over - Meet donor eligibility or suitability according to institutional standards. If the donor is deemed ineligible according to Foundation for the Accreditation of Cellular Therapy (FACT) standards, but is suitable for donation per institutional standards, the donor will be eligible for the protocol Exclusion Criteria: - 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.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes
Given intravenously
Allogeneic Adenovirus-specific Cytotoxic T Lymphocytes
Given intravenously

Locations

Country Name City State
United States Nationwide Children's Hospital Columbus Ohio
United States Ohio State University Comprehensive Cancer Center Columbus Ohio

Sponsors (1)

Lead Sponsor Collaborator
Sumithira Vasu

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 Antiviral activity defined as response to viral load Complete response, partial response, stable disease or progression will be defined and proportion of each outcome will be calculated. At day 28
Secondary Persistence of infused CTLs as measured by T cell gene rearrangement and effects on clinical signs of viral infection Up to 1 year
Secondary Overall survival Kaplan-Meier survival function will be used to estimate the survival probability. From last CTL infusion till death, assessed at 6 and 12 months
Secondary Risk for chronic GVHD Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated. At 6 and 12 months post CTL infusion
Secondary Systemic infections Will be reported by etiologic agent, site of disease, date of onset, and severity. Within 6 months of CTL infusion
Secondary Secondary graft failure Proportion of secondary graft failure for both populations will be assessed at 30 days post CTL infusion will be calculated and 95% confidence intervals will be estimated accordingly. 30 days post-CTL infusion
Secondary Effects of cytomegalovirus (CMV) specific-CTL on viral loads assessed by weekly reverse transcriptase-polymerase chain reaction Up to 1 year
Secondary Viral reactivations Proportion of viral reactivations within 6 months will be calculated and 95% confidence intervals will be estimated accordingly. Up to 6 months
Secondary Clinical response to CTL infusions At 6 weeks and 3 months
Secondary Number of participants with treatment-related adverse events as assessed by CTCAE v4.0". Up to 1 year
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