- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03665675
Donor Virus-Specific CMV or AdV CTL to Treat CMV or AdV Reactivation or Disease After Solid Organ or HCT
Pilot Study of Haploidentical or Matched Donor Virus-Specific T-cells (Cytomegalovirus (CMV) or Adenovirus (AdV)) to Treat CMV or AdV Reactivation or Disease in Patients After Solid Organ or Hematopoietic Stem Cell Transplantation (HCT)
Study Overview
Status
Conditions
Detailed 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.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: The Ohio State University Comprehensive Cancer Center
- Phone Number: 800-293-5066
- Email: OSUCCCClinicaltrials@osumc.edu
Study Contact Backup
- Name: Nicole Szuminski
- Phone Number: 614-688-9796
- Email: Nicole.Szuminski@osumc.edu
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43205
- Recruiting
- Nationwide Children's Hospital
-
Contact:
- Chris Ouellette, MD
-
Contact:
- Melinda Triplet, RN, BSN
- Phone Number: 614-722-6039
- Email: Melinda.Triplet@nationwidechildrens.org
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Columbus, Ohio, United States, 43210
- Recruiting
- Ohio State University Comprehensive Cancer Center
-
Contact:
- Sumithira Vasu, MBBS
- Phone Number: 614-293-3196
- Email: Sumithira.Vasu@osumc.edu
-
Principal Investigator:
- Sumithira Vasu, MBBS
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (CMV-specific CTLs)
Participants receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes IV.
Participants with persistent infection are eligible for second infusion after 28 days.
|
Given intravenously
|
Experimental: Treatment (AdV-specific CTLs)
Patients receive allogeneic adenovirus-specific cytotoxic T Lymphocytes IV.
Participants with persistent infection are eligible for second infusion after 28 days.
|
Given intravenously
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0
Time Frame: Up to 30 days post infusion
|
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
Time Frame: Up to 1 year
|
Up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antiviral activity defined as response to viral load
Time Frame: At day 28
|
Complete response, partial response, stable disease or progression will be defined and proportion of each outcome will be calculated.
|
At day 28
|
Persistence of infused CTLs as measured by T cell gene rearrangement and effects on clinical signs of viral infection
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Overall survival
Time Frame: From last CTL infusion till death, assessed at 6 and 12 months
|
Kaplan-Meier survival function will be used to estimate the survival probability.
|
From last CTL infusion till death, assessed at 6 and 12 months
|
Risk for chronic GVHD
Time Frame: At 6 and 12 months post CTL infusion
|
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
|
Systemic infections
Time Frame: Within 6 months of CTL infusion
|
Will be reported by etiologic agent, site of disease, date of onset, and severity.
|
Within 6 months of CTL infusion
|
Secondary graft failure
Time Frame: 30 days post-CTL infusion
|
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
|
Effects of cytomegalovirus (CMV) specific-CTL on viral loads assessed by weekly reverse transcriptase-polymerase chain reaction
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Viral reactivations
Time Frame: Up to 6 months
|
Proportion of viral reactivations within 6 months will be calculated and 95% confidence intervals will be estimated accordingly.
|
Up to 6 months
|
Clinical response to CTL infusions
Time Frame: At 6 weeks and 3 months
|
At 6 weeks and 3 months
|
|
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0".
Time Frame: Up to 1 year
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sumithira Vasu, MBBS, Ohio State University Comprehensive Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OSU-17199
- NCI-2018-01412 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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