SARS-CoV-2 Donor-Recipient Immunity Transfer

NCT04666025 | Completed DMC

• 3 other identifiers: 20153NCI-2020-11156P30CA033572
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• SARS-CoV-2 IgA concentration

  Up to 180 days post-HCT

Other Outcomes (1)

• SARS-CoV-2 -specific T cell memory profile and associated function

  Up to 180 days post-HCT

Study Arms (1)

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.

Procedure: Biospecimen Collection; Other: Diagnostic Laboratory Biomarker Analysis; Other: Electronic Health Record Review; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of nasopharyngeal swabs, blood, and saliva samples

Observational (biospecimen collection, medical chart review)

Diagnostic Laboratory Biomarker Analysis OTHER

Correlative studies

Observational (biospecimen collection, medical chart review)

Electronic Health Record Review OTHER

Medical charts are reviewed

Observational (biospecimen collection, medical chart review)

Questionnaire Administration OTHER

Complete questionnaire

Observational (biospecimen collection, medical chart review)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (2)

• La Rosa C, Chiuppesi F, Park Y, Zhou Q, Yang D, Gendzekhadze K, Ly M, Li J, Kaltcheva T, Ortega Francisco S, Gutierrez MA, Ali H, Otoukesh S, Amanam I, Salhotra A, Pullarkat VA, Aldoss I, Rosenzweig M, Aribi AM, Stein AS, Marcucci G, Dadwal SS, Nakamura R, Forman SJ, Al Malki MM, Diamond DJ. Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study. Front Immunol. 2023 Mar 3;14:1114131. doi: 10.3389/fimmu.2023.1114131. eCollection 2023.

  PMID: 36936918 DERIVED

• La Rosa C, Chiuppesi F, Park Y, Gendzekhadze K, Zhou Q, Faircloth K, Kaltcheva T, Johnson D, Ortega Francisco S, Amanam I, Otoukesh S, Pullarkat VA, Nakamura R, Diamond DJ, Forman SJ, Al Malki MM. Adoptive transfer of functional SARS-COV-2-specific immunity from donor graft to hematopoietic stem cell transplant recipients. Am J Hematol. 2022 Nov;97(11):E404-E407. doi: 10.1002/ajh.26691. Epub 2022 Sep 2. No abstract available.

  PMID: 36053823 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Nasopharyngeal swabs, blood, saliva

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Chronic-Phase; COVID-19; Hematologic Neoplasms; Hodgkin Disease; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Site; Lymphoma

Study Officials

• Monzr M Al Malki

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 14, 2020
• Study Start: September 23, 2020
• Primary Completion: May 5, 2023
• Study Completion: May 5, 2023
• Last Updated: April 8, 2024

Record last verified: 2024-04

Locations

US (1)