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Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

Primary Purpose

Cytomegalovirus, Adenovirus

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

VST infusion

CliniMACS

About this trial

This is an interventional treatment trial for Cytomegalovirus

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients who have undergone haploidentical HCT or a matched-sibling/matched-unrelated donor HCT, and have CMV and/or ADV detected by PCR in the peripheral blood refractory to antiviral therapy per institutional BMTCT SOP 20.05. Definition of "refractory" viremia is persistent positive CMV or ADV viremia after 14 days of treatment per institutional SOP, or an increasing copy number (≥1 log) after 7 days of treatment. Patients have no suspected or confirmed GVHD. Availability of haploidentical donor for isolation of virus-specific T-cells. Have not received a Donor Lymphocyte Infusion in the past 4 weeks. Female patients of childbearing age must have a negative pregnancy test. Subject, parent, or guardian are capable of giving signed informed consent. Patients must have a shortening fraction >26% or left ventricular ejection fraction >40%. Patients must have a bilirubin less than or equal to 2.5mg/dL and alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal. Patients must have an estimated glomerular filtration rate (GFR) greater than 60mL/min/1.73m2. Patients must be free of severe infection which upon determination of the principal investigator precludes therapy with VST. Patients must have FVC >50% predicted or if unable to perform pulmonary function testing must maintain pulse oximetry saturation > 92% on room air. Patients must have engrafted with an ANC >500 cells/mm3 for 3 consecutive days. Inclusion criteria for donors Age ≥18 years. At least single haplotype matched (≥3/6) family member. Donor will be identical to the stem cell donor (Cohort A) or different from the stem cell donor (Cohort B). HIV negative. For females of childbearing age: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment AND not lactating with intent to breastfeed. Regarding donation eligibility, is identified as either having completed the process of donor eligibility determination as outlined in 21CFR 1271 and agency guidance or does not meet 21CFR 1271 eligibility requirements but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21CFR. Identified recipient with CMV and/or ADV reactivation post-HCT. Exclusion Criteria: Active GVHD. Pregnancy. Inability to provide consent. Need for vasopressor or ventilatory support Patients receiving steroids >0.5 mg/kg prednisone equivalent at the time of VST infusion Donor Lymphocyte Infusion within 4 weeks prior to VST infusion. Receipt of Thymoglobulin or Alemtuzumab within 30 days of VST infusion.

Sites / Locations

St . Jude Children's Research HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort A

Cohort B

Arm Description

Cohort A will include haploidentical donor who is identical to the stem cell donor. The first 5 patients will be enrolled in Cohort A. If safety criteria are met, cohort B will be open for enrollment.

Cohort B will include haploidentical donor who is different from the stem cell donor

Outcomes

Primary Outcome Measures

Degree of reduction of CMV and/or ADV viral load

The primary objective of this clinical study is to evaluate the efficacy of adoptively transferred CMV- and ADV-specific haploidentical T-cells in patients who have undergone allogeneic HCT. This primary endpoint is defined as ≥1 log10 reduction in CMV and/or ADV viral load 4 weeks after VST infusion. When the initial viral load is <1 log10 above the threshold of detection the endpoint will be a reduction to below the threshold of detection. The success rate will be evaluated using descriptive statistics (sample proportion and standard error). Patients with both CMV and ADC detected will count as success if reduction occurs in one or both of CMV and ADV.

Secondary Outcome Measures

Incidence of infusion-related grade 3-5 adverse events 24 hours after infusion

The incidence of infusion-related grade 3-5 adverse events will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Incidence of AEs related to grade 3-4 cytokine release syndrome (CRS), or grade 1-2 CRS persist beyond 72 hours despite therapy

The incidence of AEs related to grade 3-4 cytokine release syndrome (CRS), or grade 1-2 CRS persist beyond 72 hours despite therapy will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Incidence of Grade 3-4 Neurotoxicity of any duration

The incidence of Grade 3-4 Neurotoxicity of any duration will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Incidence of Grade 3-4 GVHD

The incidence of Grade 3-4 GVHD will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Incidence of grade 3-5 non hematologic toxicities attributable to VST

The incidence of grade 3-5 non hematologic toxicities attributable to VST will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Incidence of secondary graft failure attributable to VST

The incidence of secondary graft failure attributable to VST will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Proportion of patients who achieve a negative viral load result at 3 months

The proportion of patients who achieve a negative viral load result at 3 months will be assessed using descriptive statistics (sample proportions with standard errors)

Persistence of response at 6 months post-infusion

The persistence of response at 6 months post-infusion will be assessed using descriptive statistics (sample proportions with standard errors)

Full Information

NCT ID

NCT05664126

First Posted

December 15, 2022

Last Updated

October 17, 2023

Sponsor

St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05664126

Brief Title

Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

Official Title

Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 1, 2023 (Actual)

Primary Completion Date

December 31, 2026 (Anticipated)

Study Completion Date

December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The investigators want to learn if CMV- and ADV-specific T-cells (cells that fight infections) isolated (selected) from a donor using an automated medical device can be a safe treatment for treating patients with CMV, and ADV after transplant.This study will test the effects and safety of giving VSTs produced here at St. Jude in treating the participant's infection. Primary objective To determine the efficacy of VSTs to achieve a ≥1 log10 reduction in CMV and/or ADV viral load in the peripheral blood 4 weeks after VST infusion. When the initial viral load is <1 log10 above the threshold of detection, the objective is to achieve a reduction to below the threshold of detection. Secondary objectives Determine the safety of VSTs when used to treat CMV and/or ADV viremia post-HCT. Determine the proportion of patients who achieve a negative viral load at 3 months post-infusion. Assess the persistence of response for 6 months post-infusion.

Detailed Description

The study will have 2 cohorts. Cohort A will include haploidentical donor who is identical to the stem cell donor. Cohort B will include haploidentical donor who is different from the stem cell donor. Seropositive donors will be screened for the presence of CMV- and ADV-specific T-cells using a functional flow cytometry assay. The donor will be considered suitable if the percentage of CD3+/IFN-γ+ cells is greater than 0.01% of CD3+ T-cells. Donor leukocytes will be collected using the Spectra Optia system. CMV- and ADV-specific T-cells will be isolated from donor leukocytes by 'IFN-γ-capture' technology using the Prodigy device over a 24-36 hour period and infused.

6. Conditions and Keywords

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

Cytomegalovirus, Adenovirus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort A

Arm Type

Experimental

Arm Description

Arm Title

Cohort B

Arm Type

Experimental

Arm Description

Cohort B will include haploidentical donor who is different from the stem cell donor

Intervention Type

Drug

Intervention Name(s)

VST infusion

Other Intervention Name(s)

The product is a suspension of allogenic peripheral blood VSTs enriched based on their secretion of IFN-γ after stimulation with the appropriate antigen

Intervention Description

single intravenous (IV) infusion.

Intervention Type

Device

Intervention Name(s)

CliniMACS

Other Intervention Name(s)

ClinMACS Prodigy

Intervention Description

Cells infusions are prepared using the ClinMACS

Primary Outcome Measure Information:

Title

Degree of reduction of CMV and/or ADV viral load

Description

Time Frame

4 weeks after VST infusion

Secondary Outcome Measure Information:

Title

Incidence of infusion-related grade 3-5 adverse events 24 hours after infusion

Description

The incidence of infusion-related grade 3-5 adverse events will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Time Frame

24 hours after infusion

Title

Incidence of AEs related to grade 3-4 cytokine release syndrome (CRS), or grade 1-2 CRS persist beyond 72 hours despite therapy

Description

Time Frame

4 weeks after VST infusion

Title

Incidence of Grade 3-4 Neurotoxicity of any duration

Description

The incidence of Grade 3-4 Neurotoxicity of any duration will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Time Frame

4 weeks after VST infusion

Title

Incidence of Grade 3-4 GVHD

Description

The incidence of Grade 3-4 GVHD will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Time Frame

4 weeks after VST infusion

Title

Incidence of grade 3-5 non hematologic toxicities attributable to VST

Description

The incidence of grade 3-5 non hematologic toxicities attributable to VST will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Time Frame

4 weeks after VST infusion

Title

Incidence of secondary graft failure attributable to VST

Description

The incidence of secondary graft failure attributable to VST will be estimated using descriptive statistics (sample proportions and cumulative incidence curves with standard errors)

Time Frame

4 weeks after VST infusion

Title

Proportion of patients who achieve a negative viral load result at 3 months

Description

The proportion of patients who achieve a negative viral load result at 3 months will be assessed using descriptive statistics (sample proportions with standard errors)

Time Frame

3 months after VST infusion

Title

Persistence of response at 6 months post-infusion

Description

The persistence of response at 6 months post-infusion will be assessed using descriptive statistics (sample proportions with standard errors)

Time Frame

6 months after VST infusion

10. Eligibility

Sex

All

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

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

Ashok Srinivasan, MD

Phone

866-278-5833

referralino@stjude.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ashok Srinivasan, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St . Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ashok Srinivasan, MD

Phone

866-278-5833

referralinfo@stjude.org

First Name & Middle Initial & Last Name & Degree

Ashok Srinivasan, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

IPD Sharing Time Frame

Data will be made available at the time of article publication.

IPD Sharing Access Criteria

Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

Clinical Trials Open at St.Jude

Learn more about this trial

Haplo-identical Viral-Specific T-cells for Treatment of Cytomegalovirus and Adenovirus Infections After Hematopoietic Cell Transplantation

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