Effectiveness of COVID-19 Vaccine in Hematopoietic Stem Cell Transplant Patients (ESCVHSCT)

Evaluation of COVID-19 Vaccine Effectiveness and Immunogenicity in Patients Receiving Hematopoietic Stem Cell Transplantation

COVID-19 vaccinations are predicted to be a huge success in pandemic control. However, the majority of the studies were conducted on healthy individuals, and the efficiency of COVID-19 vaccination in post-transplant patients is uncertain. In the setting of HSCT, the extreme immunosuppression caused by the conditioning regimen and the graft versus host disease (GvHD) preventive regimen clearly has an impact on the efficacy and immunogenicity of the COVID-19 vaccine. Given the importance of eliciting early SARS-Cov-2 protective immunity in patients who are undergoing Allo-HSCT and the EBMT recommendation to endorse vaccination as early as 3 months after allo-HCT [7], we conduct this prospective study to investigate the safety and immunogenicity of three doses Pastucovac (an RBD-based SARS-Cov-2 vaccine) at the early post-transplant period in adult Iranian patients who are undergoing Allo-HSCT. We also want to see whether there are any possible predictors, such as the effect of clinical characteristics and lymphocyte subpopulations at the time of vaccination on the serologic response following immunization. The findings of this study will serve to guide future COVID-19 vaccination recommendations in this population, such as the optimal starting time, interval time, and so on.

Study Overview

• Status: Recruiting
• Conditions: COVID-19 Vaccines; Hematopoietic Stem Cell Transplantation (HSCT); Immune System Tolerance
• Intervention / Treatment: Biological: Pasocovac vaccine

Detailed Description

From the start of the study until the sample size of 100 patients is attained, all consecutive adult patients who are candidates for Allo-SCT at HORCSCT, sign a research project consent to administer SARS-CoV-2 vaccination with Pastucovac, and sign a permission to take pre-and post-vaccination blood samples for deposit to the research database, are enrolled in the study. At baseline (before conditioning) and day +30 post-transplant, peripheral blood samples are taken to test particular lymphocyte subpopulations and SARS-CoV-2 IgG titers.

All enrolled post-Allo-SCT participants who meet the inclusion criteria including; age ≥ 18 years, successfully engraftment with full donor chimerism, absence of grade 3,4 acute GvHD or severe extensive chronic GvHD, no receive more than 0.5 mg/kg prednisolone, and no positive RT-PCR test for COVID-19 following HSCT are recruited to study from 3 to 12 months after Allo-HSCT and vaccinated with 2 doses of Pastucovac, with a 4-week (±7 days) interval and a booster dose with an 8-week (±7 days) interval from the second dose. Peripheral blood samples are collected before the first dose of vaccine to assess certain immune reconstitution and SARS-CoV-2 IgG titer. The serologic response against the SARS-CoV-2 spike protein (anti-S) is assessed in serum four weeks (± one week) after the first vaccine dose (before the second vaccine), four weeks (± one week) after the second dose, and four weeks (± one week) after the booster dose (third dose).

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maryam Barkhordar, MD; Phone Number: 0098 913 1856733; Email: barkhordarm.n@gmail.com
• Study Contact Backup: Name: Leila Sharifi Aliabadi, Master; Phone Number: 0098 912 549 2213; Email: ctu@sina.tums.ac.ir

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1417713135
    • Recruiting
    • Hematology, Oncology, and Stem Cell Transplantation Research Center of shariaty Hospital
    • Contact: Maryam Barkhordar; Phone Number: 0098 9131856733; Email: barkhordarm.n@gmail.com
    • Principal Investigator: Bahram Chahardovali, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age ≥ 18 years, successfully engraftment with full donor chimerism, absence of grade 3,4 acute GvHD or severe extensive chronic GvHD, no receive more than 0.5 mg/kg prednisolone, and no positive RT-PCR test for COVID-19 following HSCT

Exclusion Criteria:

Patients who are not candidates for the COVID-19 vaccine after transplantation due to severe complications.

Patients who do not consent to vaccination after transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vaccine; Patients who are a candidate for HSCT within the the Hematology, Oncology, and Stem Cell Transplantation Research Center of Shariaty Hospital, and agree to be vaccinated with an approved vaccine against the COVID-19 virus.	Biological: Pasocovac vaccine; All enrolled post-Allo-SCT participants who meet the inclusion criteria are recruited to study from 3 to 12 months after Allo-HSCT and vaccinated with 2 doses of Pastucovac, with a 4-week (±7 days) interval and a booster dose at an 8-week (±7 days) interval from the second dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of COVID-19 vaccine effectiveness	defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer	4 weeks (±7 days) post second COVID-19 vaccine
Grade III-IV vaccine-related adverse reactions	Prevalence of reactogenicity, Serious Adverse Events (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR)	14 days after administration of each vaccine dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Graft versus host disease (GvHD)	Measuring how the acute GvHD affect the response to the vaccine	4-week (±7 days) after second and third (booster) dose of vaccine.
GvHD prophylactic strategy affect immunological response	Measuring how early prophylactic immuno-suppression tapering affect the response to the vaccine	4-week (±7 days) after third (booster) dose of vaccine.
Immune cells recovery predicting the response to the COVID-19 vaccine	Measuring how early post HSCT Immune subsets reconstitution including T cells, NK cells, and B cells predict the seroconversion after second dose of vaccine.	4-week (±7 days) after third (booster) dose of vaccine.
seroconversion after second dose of vaccine	defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer in patients starting their vaccination course 3-6 months after HSCT	4-week (±7 days) after second dose of vaccine.
seroconversion after second dose of vaccine	defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer in patients starting their vaccination course 6-12 months after HSCT.	4-week (±7 days) after second dose of vaccine.
seroconversion after first dose of vaccine	defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer	4-week (±7 days) after first dose of vaccine.
seroconversion after third (booster) dose of vaccine	defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer	4-week (±7 days) after third (booster) dose of vaccine.
Incidence and severity of COVID-19 infections	Determine incidence and severity of COVID-19 infections by 6 months following immunization with a SARS-CoV-2 vaccine.	6 months following start of immunization
Correlation of seroconversion with patient characteristics	Determine how the patients characteristics including age, sex, performance score, and underlying disease affect on seroconversion	4-week (±7 days) after second and third (booster) dose of vaccine.

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Maryam Barkhordar, MD, Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation, SARS-CoV-2 specific IgG , immune reconstitution, COVID-19 vaccine efficacy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 1400-2-101-54534

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No