SARS-CoV-2 Donor-Recipient Immunity Transfer

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

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.

Study Overview

• Status: Completed
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Acute Myeloid Leukemia; Hodgkin Lymphoma; Myelofibrosis; Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; COVID-19 Infection; Accelerated Phase CML, BCR-ABL1 Positive; Chronic Phase CML, BCR-ABL1 Positive
• Intervention / Treatment: Other: Diagnostic Laboratory Biomarker Analysis; Other: Questionnaire Administration; Other: Electronic Health Record Review; Procedure: Biospecimen Collection

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients (donors and recipients) scheduled to undergo a standard of care donor HCT procedure.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Observational (biospecimen collection, medical chart review); 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.

Other: Diagnostic Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Complete questionnaire; Other: Electronic Health Record Review; Medical charts are reviewed; Procedure: Biospecimen Collection; Undergo collection of nasopharyngeal swabs, blood, and saliva samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Monzr M Al Malki, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): May 5, 2023
• Study Completion (Actual): May 5, 2023

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Leukemia, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Chronic Disease; Neoplasms; Lymphoma; COVID-19; Myelodysplastic Syndromes; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Accelerated Phase; Myeloproliferative Disorders
• Other Study ID Numbers: 20153 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2020-11156 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No