SARS-CoV-2 Donor-Recipient Immunity Transfer

Acute Myeloid Leukemia Clinical Trial

Official title:

Observational Study of SARS-CoV-2 Donor-Recipient Immunity Transfer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04666025
• Other study ID #: 20153
• Secondary ID: NCI-2020-1115620
• Status: Completed
• Start date: September 23, 2020
• Est. completion date: May 5, 2023

Study information

• Verified date: April 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study investigates whether donors with previous exposure to COVID-19 can pass their immunity by hematopoietic (blood) stem cell transplant (HCT) donation to patients that have not been exposed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes the COVID19 infection. This study may provide critical information for medical decision-making and possible immunotherapy interventions in immunocompromised transplant recipients, who are at high risk for COVID19 severe illness.

Description:

PRIMARY OBJECTIVE:

I. To establish the possibility of anti-SARS-CoV-2 adaptive immunity transfer from matched related (MRD) or unrelated (MUD) HCT donor to HCT recipient.

SECONDARY OBJECTIVES:

I. To explore anti-SARS-CoV-2 adaptive immunity transfer in the haploidentical (haplo) HCT setting.

II. To assess the prevalence and change over time of SARS-CoV-2 seropositive donors among all consented donors.

OUTLINE:

DONORS: Prior to HCT, sibling donors (MRD and haplo) undergo a nasopharyngeal swab per standard of care for SARS-Cov-2 testing. For MUD donors, initial testing may consist of a questionnaire. All donors undergo collection of blood and saliva at the time of granulocyte-colony stimulating factor (G-CSF). Donors' medical charts are also reviewed.

RECIPIENTS: Patients undergo a nasopharyngeal swab for SARS-Cov-2 testing at 30, 60, 90, 120 days post-HCT, and afterwards as deemed necessary by the treating physician. Patients also undergo the collection of blood and saliva specimens at days 30, 60, 90, 120, 150, and 180 post-HCT. Recipients' medical charts are also reviewed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 5, 2023
• Est. primary completion date: May 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ALL COHORTS: Documented written informed consent of the participant

• ALL COHORTS: Recipients must have a planned allogeneic HCT procedure. MRD, MUD, and haplo HCT allowed. Usage of post-transplant cyclophosphamide (PTCy) permitted only in haplo setting

• ALL COHORTS: GCSF-mobilized peripheral blood stem cell (PBSC) only as graft source

• ALL COHORTS: Planned HCT with minimal to no-T cell depletion of graft for the treatment of the following hematologic malignancies:

• Lymphoma (Hodgkin and non-Hodgkin)

• Myelodysplastic syndrome

• Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in hematologic remission by bone marrow and peripheral blood. Persistent lymphadenopathy on computed tomography [CT] or CT/positron emission tomography [PET] scan without progression is allowed)

• Acute myeloid leukemia in first or second remission

• Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase

• Other hematologic malignancies including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis

• ALL COHORTS: Willingness to

• Provide blood samples and saliva specimens

• Permit medical record review

• ADDITIONAL CRITERIA FOR RECIPIENTS IN THE MAIN COHORT:

• Absence of documented COVID-19 history and active COVID-19 infection

• ADDITIONAL CRITERIA FOR RECIPIENTS IN THE REFERENCE COHORT: Active COVID-19 infection during HCT

Related Conditions & MeSH terms

• Accelerated Phase CML, BCR-ABL1 Positive
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Chronic Phase CML, BCR-ABL1 Positive
• COVID-19
• COVID-19 Infection
• Hematopoietic and Lymphoid Cell Neoplasm
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoblastic Lymphoma
• Lymphoma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Myelofibrosis
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Non-Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of nasopharyngeal swabs, blood, and saliva samples

Other:
• Diagnostic Laboratory Biomarker Analysis
Correlative studies
• Electronic Health Record Review
Medical charts are reviewed
• Questionnaire Administration
Complete questionnaire

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SARS-CoV-2 -specific T cell memory profile and associated function	The data analysis for estimating the effect of donor immunity transfer on functional cellular immunity through time will be exploratory in nature and will focus on graphical display and summary statistics. Longitudinal levels of T cells specific for SARS-CoV-2 S or SARS-CoV-2 N antigens will be measured as a correlate of immunity transfer efficiency.	Up to 180 days post-HCT
Primary	Severe acute respiratory syndrome (SARS)-Coronavirus 2 (CoV-2) Spike protein (S)-specific IgG concentration and T cell levels	Testing for SARS-CoV-2 antibodies will be performed on serum samples using in house developed enzyme-linked immunosorbent assay (ELISA). The qualitative assays will be developed to investigate Spike subunit 1 (S1)-specific antibodies of the IgG, IgM and IgA subclasses in serum and saliva samples. All SARS-Cov-2 seropositive donor-HCT recipient pairs patients will undergo cellular immunogenicity evaluations using flow cytometry. The data analysis for estimating the effect of donor immunity transfer on functional cellular immunity through time will be exploratory in nature and will focus on graphical display and summary statistics. Longitudinal levels of T cells specific for SARS-CoV-2 S will be measured as a correlate of immunity transfer efficiency.	Up to 180 days post-hematopoietic stem cell transplant (HCT)
Primary	SARS-CoV-2 nucleocapsid protein (N) -specific IgG concentration and T cell levels	Testing for SARS-CoV-2 antibodies will be performed on serum samples using in house developed ELISA. The qualitative assays will be developed to investigate nucleocapsid (N)-specific antibodies of the IgG, IgM and IgA subclasses in serum and saliva samples. All SARS-Cov-2 seropositive donor-HCT recipient pairs patients will undergo cellular immunogenicity evaluations using flow cytometry. The data analysis for estimating the effect of donor immunity transfer on functional cellular immunity through time will be exploratory in nature and will focus on graphical display and summary statistics. Longitudinal levels of T cells specific for SARS-CoV-2 N antigens will be measured as a correlate of immunity transfer efficiency.	Up to 180 days post-HCT
Primary	SARS-CoV-2 neutralizing antibodies	Evaluation of SARS-CoV-2 neutralizing antibody titers in serum samples will be performed using SARS-CoV-2 lentiviral-pseudovirus based on published protocols. Spike incorporation into the pseudovirus will be verified and quantified by western blot using Spike-specific antibodies (Sino Biological) and by ELISA using Spike Detection kit (Sino Biological), respectively.	Up to 180 days post-HCT
Secondary	SARS-CoV-2 IgA concentration	Testing for SARS-CoV-2 antibodies will be performed on serum samples using in house developed ELISA.	Up to 180 days post-HCT