Viral Specific T-Lymphocytes to Treat Adenovirus or CMV

NCT04364178 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 69251
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Adenovirus; Cytomegalovirus Infections

Keywords

Cytokine Capture System; Adenovirus; Cytomegalovirus; Hematopoietic Cell Transplant; Solid Organ Transplant; Immunocompromised; Inborn Error of Immunity

Outcome Measures

Primary Outcomes (2)

• Grade III-IV Acute Graft versus host disease

  The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.

  Day 0 through 90 days after last cellular infusion

• CTCAE Grade 4/5 Adverse Events

  The incidence of patients who develop CTCAE Grade 4/5 Adverse events

  Day 0 through 30 days from last cellular infusion

Secondary Outcomes (10)

• 6-month Survival (continuous)

  First cellular infusion to 6 months post first cellular infusion

• Viral load by Polymerase Chain Reaction (PCR)

  Baseline through study completion, an average of 6 months

• Viral load from Respiratory Viral Panel (RVP)

  Baseline through study completion, an average of 6 months

• Viral load from Bronchoalveolar lavage (BAL)

  Baseline through study completion, an average of 6 months

• Viral load from Urine

  Baseline through study completion, an average of 6 months

Study Arms (1)

Viral Specific T-Lymphocytes

EXPERIMENTAL

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.

Biological: Adenovirus Specific T- Lymphocytes; Biological: Cytomegalovirus Specific T-Lymphocytes

Interventions

Adenovirus Specific T- Lymphocytes 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.

Viral Specific T-Lymphocytes

Cytomegalovirus Specific T-Lymphocytes 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.

Viral Specific T-Lymphocytes

Eligibility Criteria

• Age: 1 Month - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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).
• Active acute GVHD grades II-IV.
• Active severe chronic GVHD.
• 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.
• Active and uncontrolled relapse of malignancy.
• Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.
• Patients who are pregnant or lactating.
• 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.
• Patients who are pregnant
• Patients who are HIV positive
• Uncontrolled infection
• Deemed high risk due to pre-existing medical condition

Sponsors & Collaborators

• Jessie L. Alexander: lead

Study Sites (2)

Jessie Alexander

Palo Alto, California, 94304, United States

Location

Lucile Packard Children's Hospital

Palo Alto, California, 94305, United States

Location

MeSH Terms

Conditions

Adenoviridae Infections; Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections; Herpesviridae Infections

Study Officials

• Jessie Alexander, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor of Pediatrics

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: August 12, 2020
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): January 1, 2032
• Last Updated: May 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)