Viral Specific T-Lymphocytes to Treat Adenovirus or CMV
- Conditions
- Cytomegalovirus InfectionsAdenovirus
- Interventions
- Biological: Adenovirus Specific T- LymphocytesBiological: Cytomegalovirus Specific T-Lymphocytes
- Registration Number
- NCT04364178
- Lead Sponsor
- Jessie L. Alexander
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 25
Not provided
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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).
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Active acute GVHD grades II-IV.
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Active severe chronic GVHD.
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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.
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Active and uncontrolled relapse of malignancy.
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Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.
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Patients who are pregnant or lactating.
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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.
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Donor Exclusion Criteria
- Patients who are pregnant
- Patients who are HIV positive
- Uncontrolled infection
- Deemed high risk due to pre-existing medical condition
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Viral Specific T-Lymphocytes 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 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. Viral Specific T-Lymphocytes 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 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.
- Primary Outcome Measures
Name Time Method Grade III-IV Acute Graft versus host disease Day 0 through 90 days after last cellular infusion The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.
CTCAE Grade 4/5 Adverse Events Day 0 through 30 days from last cellular infusion The incidence of patients who develop CTCAE Grade 4/5 Adverse events
- Secondary Outcome Measures
Name Time Method Viral load by Polymerase Chain Reaction (PCR) Baseline through study completion, an average of 6 months The pace at which the viral load is undetectable in whole blood or plasma
Antiviral Agents Day 0 through study completion, an average of 6 months The introduction of concomitant antiviral medication post infusion, if any
Immune Reconstitution Baseline through study completion, an average of 6 months The pace of systemic immune reconstitution
6-month Survival (continuous) First cellular infusion to 6 months post first cellular infusion Number of deaths that occurred from treatment
Viral load from Bronchoalveolar lavage (BAL) Baseline through study completion, an average of 6 months The pace at which the viral load is undetectable from bronchial washing
Viral load from Stool Baseline through study completion, an average of 6 months The pace at which the viral load is undetectable from stool sample
Viral load from fluid/tissue Baseline through study completion, an average of 6 months The pace at which the viral load is undetectable from other fluid/tissue sample
Clinical response to viral specific infusion Baseline through study completion, an average of 6 months as clinically indicated By imaging and symptomatology
Viral load from Respiratory Viral Panel (RVP) Baseline through study completion, an average of 6 months The pace at which the viral load is undetectable from nasopharyngeal swab
Viral load from Urine Baseline through study completion, an average of 6 months The pace at which the viral load is undetectable from urine sample
Trial Locations
- Locations (2)
Jessie Alexander
🇺🇸Palo Alto, California, United States
Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States