Viral Specific T-Lymphocytes to Treat Adenovirus or CMV

NCT ID: NCT04364178

Last Updated: 2024-05-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-12
• Study Completion Date: 2032-01-01

Brief Summary

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥2/6 HLA-matched, viral specific T cells have efficacy against adenovirus and CMV in subjects who have previously received any type of allogeneic HCT or solid organ transplant (SOT), or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus and CMV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. In this trial, we will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus or CMV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.

Detailed Description

If a subject shows a partial response, defined as a decrease in viral load of at least 50% from baseline or 50% improvement of clinical signs and symptoms, or no response, they are eligible to receive up to 4 additional cellular infusions from the same donor, at a minimum of 14-day intervals. If the same donor is no longer available, eligible, or appropriate, another donor may be considered for a maximum of 4 total cellular infusions at the discretion of the study PI and treating physician. A subject will not exceed a maximum of 5 total infusions from 2 donors.

Subjects are followed for 1 year post initial viral-specific T cell infusion. If subjects receive additional infusion(s), GvHD and adverse events will be followed for an additional 90 days from last infusion. Data may be abstracted from subjects' medical charts for an additional 1 year after most recent viral-specific T cell infusion.

Conditions

Adenovirus; Cytomegalovirus Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Viral Specific T-Lymphocytes

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.

Group Type: EXPERIMENTAL

Adenovirus Specific T- Lymphocytes

Intervention Type: BIOLOGICAL

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Adenovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.

Cytomegalovirus Specific T-Lymphocytes

Intervention Type: BIOLOGICAL

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Cytomegalovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.

Interventions

Adenovirus Specific T- Lymphocytes

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Adenovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.

Intervention Type: BIOLOGICAL

Cytomegalovirus Specific T-Lymphocytes

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Cytomegalovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

1. Received ATG or Alemtuzumab within 28 days of viral-specific T cell infusion and a lack of evidence of T cell survival, defined by <10 CD3+ T cells/uL (in unique situations, plasmapheresis may be considered).

2. Active acute GVHD grades II-IV.

3. Active severe chronic GVHD.

4. Received donor lymphocyte infusion, with the exception of a fraction of an umbilical cord blood, within 21 days of viral-specific T cell infusion. Subjects receiving a fraction of an umbilical cord blood within 21 days of the viral-specific T cell infusion will not be excluded.

5. Active and uncontrolled relapse of malignancy.

6. Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.

7. Patients who are pregnant or lactating.

8. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks to participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.

1. Patients who are pregnant

2. Patients who are HIV positive

3. Uncontrolled infection

4. Deemed high risk due to pre-existing medical condition

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jessie L. Alexander

OTHER

Sponsor Role: lead

Responsible Party

Jessie L. Alexander

Clinical Associate Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jessie Alexander, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Jessie Alexander

Palo Alto, California, United States

Lucile Packard Children's Hospital

Palo Alto, California, United States

Countries

United States

Other Identifiers

69251

Identifier Type: -

Identifier Source: org_study_id