Viral Specific T-Lymphocytes to Treat Adenovirus, CMV and... | NCT04364178

NCT04364178

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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 Biological: EBV Specific T-Lymphocytes

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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.

Measure	Description	Time Frame
Number of Patients With Grade III-IV Acute Graft Versus Host Disease	Cumulative 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 (last infusion occurred up to 38 days post day 0)
Number of Patients Who Experienced Grade 4/5 Adverse Events After Infusion	Cumulative number of patients with CTCAE Grade 4/5 Adverse events which occurred after infusion	Day 0 through 90 days after last cellular infusion (last infusion occurred up to 38 days post day 0)

Measure	Description	Time Frame
Number of Patients Who Reached 6 Month Survival	Cumulative number of patients surviving at 6 months	First cellular infusion to 6 months post first cellular infusion (last infusion occurred up to 38 days post day 0)
Number of Patients Who Achieved One Year Survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Patient, parent, or legal guardian must have given written informed consent, according to FDA guidelines. For patients ≥ 7 years of age who are developmentally able, assent or affirmation will be obtained, if feasible.
Male or female, 1 month through 65 years old, inclusive, at the time of informed consent.
Prior allogeneic hematopoietic stem cell transplant (bone marrow, peripheral blood stem cells, single or double cord blood), OR prior solid organ transplant (liver, kidney, lung and/or heart, intestinal, or multivisceral), OR diagnosis of primary immunodeficiency OR current/recent administration of immunosuppressive therapy for cancer or autoimmune disease.
Clinical status, at time of consent, amendable to tapering of steroids to less than 1 mg/kg/day prednisone (or equivalent) prior to cellular infusion.
Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized.
Diagnosis of Adenovirus or CMV infection, persistent despite standard therapy.

A. Adenovirus Infection or Disease:

Active adenovirus infection: (i.e. gastroenteritis, pneumonia, hemorrhagic cystitis, hepatitis, pancreatitis, meningitis) defined as the demonstration of adenovirus by biopsy specimen from affected site(s) (by culture or histology), or the detection of adenovirus by culture, PCR or direct fluorescent antibody stain in fluid in the presence of worsening or persistent clinical or imaging findings despite at least 14 days of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or other available pharmacological agents) OR
Refractory adenoviremia: defined as DNAemia >5000 copies/mL or <1 log decrease after at least 2 weeks of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or other available pharmacological agents) OR
Intolerance of or contraindication to antiviral medications.

B. CMV Infection or Disease:

Active CMV infection: (i.e. pneumonia, meningitis, retinitis, hepatitis, hemorrhagic cystitis, and/or gastroenteritis) defined as the demonstration of CMV by biopsy specimen from affected site(s) (by culture or histology) or the detection of CMV by culture, PCR or direct fluorescent antibody stain in fluid in the presence of worsening or persistent clinical or imaging findings despite at least 14 days of appropriate antiviral therapy (i.e. Foscarnet, ganciclovir, cidofovir, or other available pharmacological agents) OR
Refractory CMV viremia: defined as the continued presence of DNAemia, with ≥2,000 IU/mL or <1 log decrease after at least 14 days of appropriate antiviral therapy (i.e. Foscarnet, ganciclovir, cidofovir, or other available pharmacological agents) OR
Intolerance of or contraindication to antiviral medications.

C. EBV Infection or Disease:

Biopsy proven lymphoma or posttransplant lymphoproliferative disease with EBV genomes detected in tumor cells by immunocytochemistry (i.e. EBER positive) or in situ PCR, OR
Clinical or imaging findings consistent with EBV lymphoma and associated elevated EBV viral load in peripheral blood in a patient where biopsy is deemed too high risk, OR
Failure of antiviral therapy, as determined by one of the two bullets below after three weeks of anti-CD20 targeted therapy such as Rituximab.

i. There was an increase or less than 50% response at sites of lymphoma disease or lymphoproliferation. ii. There was a rise or a fall of less than 50% in EBV viral load in peripheral blood of PTLD patients.

Exclusion Criteria:

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.

Donor Inclusion Criteria

12 years of age or older
Able to understand and consent/assent to the procedure
Required hemoglobin of 11g/dL or greater
Partial (2/6 or more) HLA match to the recipient

Donor Exclusion Criteria

Donor is pregnant
Donor is HIV positive
Donor is positive for hepatitis B and/or hepatitis C
Uncontrolled infection
Deemed to be a high risk donor based on responses to donor risk questionnaire
Deemed high risk due to pre-existing medical condition or abnormal lab results

Name	Affiliation	Role
Jessie Alexander, MD	Stanford University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
UPMC (University of Pittsburgh Medical Center)		Pittsburgh	Pennsylvania	15224	United States

Arm/Group Information

ID	Title	Description
FG000	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. 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. 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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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. 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. 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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With Grade III-IV Acute Graft Versus Host Disease

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

3 of the total enrolled participants did not receive treatment after screening

Posted

Count of Participants

Participants

Day 0 through 90 days after last cellular infusion (last infusion occurred up to 38 days post day 0)

ID	Title	Description
OG000	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. 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. 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. 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. 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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment

ID	Term
D000257	Adenoviridae Infections
D003586	Cytomegalovirus Infections
D020031	Epstein-Barr Virus Infections

ID	Term
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D006566	Herpesviridae Infections