Preservation and Transfer of HBV Immunity After Allogeneic HSCT for SCD

NCT05200338 | Unknown DMC

• 1 other identifier: METC 2021_091
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Sickle cell disease (SCD) patients ending with mixed mononuclear chimerism after non-myeloablative HSCT with alemtuzumab/TBI conditioning will probably preserve their immune response to vaccinations administered prior to the transplantation and will therefore not need to be revaccinated. Furthermore, SCD patients after haploidentical HSCT might benefit from adoptive transfer of immunity from their donors. To test the first hypothesis, patients undergoing alemtuzumab/TBI HSCT will be vaccinated with a hepatitis B virus (HBV) vaccine before the transplant. To test the second hypothesis, haploidentical and matched related donors will be vaccinated prior to stem cell donation against HBV. Neither the patient nor the donor may previously have been immunized against HBV in all cohorts. Post-transplantation, the investigators will be able to evaluate whether SCD patients preserve their pre-transplant immune response in the post-transplantation period. Furthermore, the investigators will determine whether donors transfer their immunity to HSCT recipients with SCD disease.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Allogeneic stem cell transplantation; Mixed chimerism; Preservation of immunity; Adoptive transfer of immunity; Hepatitis B virus vaccination

Outcome Measures

Primary Outcomes (1)

• The proportion of SCD patients with a preserved anti-HBs response and HBV-specific cellular response following non-myeloablative allogeneic HSCT with an HBV naive MSD at 12 months post-transplantation as compared to SCD patients without HSCT.

  An antibody titer (anti-HBsAg) of \>10IU/l is considered protective.

  +1 year post-transplantation

Secondary Outcomes (4)

• The proportion of SCD patients with a preserved anti-HBs response and HBV-specific cellular response following non-myeloablative allogeneic HSCT with an HBV naive MSD at 3-, 6-, and 24 months post-transplantation as compared to SCD patients without HSCT.

  3-, 6-, and 24 months post-transplantation

• The proportion of SCD patients with a preserved anti-HBs response and HBV-specific cellular response following non-myeloablative allogeneic HSCT with an HBV naive haploidentical donor (cohort 1b) at 3-, 6-, 12- and 24 months post-transplantation.

  3-, 6-, 12- and 24 months post-transplantation

• The proportion of SCD patients with an adoptive transfer of anti-HBs response and HBV-specific cellular response following non-myeloablative haploidentical HSCT with an HBV vaccinated donor at 3-, 6-, 12- and 24- months post-transplantation (cohort 3a).

  3-, 6-, 12- and 24 months post-transplantation

• Serum total IgG level and peripheral blood T-lymphocyte subset counts (CD3+, CD4+, CD8+), B-lymphocyte subset counts (CD19+) and NK cell count, at 3-, 6-, 12- and 24-months post-transplantation as compared to counts before the start of (pre-)conditioning

  3-, 6-, 12- and 24-months post-transplantation

Study Arms (5)

Cohort 1a

OTHER

SCD patients that are vaccinated against hepatitis B virus before matched sibling donor allogeneic SCT.

Drug: Engerix-B

Cohort 1b

OTHER

SCD patients that are vaccinated against hepatitis B virus before haploidentical donor allogeneic SCT.

Drug: Engerix-B

Cohort 2

OTHER

SCD patients that are vaccinated against hepatitis B virus without undergoing allogeneic SCT (control group).

Drug: Engerix-B

Cohort 3a

OTHER

SCD patients undergoing matched sibling donor allogeneic SCT whose donor is vaccinated against hepatitis B virus before stem cell collection.

Drug: Engerix-B

Cohort 3b

OTHER

SCD patients undergoing haploidentical donor allogeneic SCT whose donor is vaccinated against hepatitis B virus before stem cell collection.

Drug: Engerix-B

Interventions

Engerix-B DRUG

Subjects are vaccinated with an accelerated scheme at 0, +1, +2 months with a booster at +12 months.

Cohort 1a; Cohort 1b; Cohort 2; Cohort 3a; Cohort 3b

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 18 or older
• High performance liquid chromatography (HPLC) confirmed diagnosis of SCD (not applicable to participating donors).
• An indication for and a planned matched sibling or haploidentical donor non-myeloablative HSCT at the Amsterdam UMC, location AMC (not applicable to patients in cohort 2 (control group) and participating donors)
• Written informed consent

You may not qualify if:

• History of either cleared, chronic or active HBV infection (positive HBsAg, anti-HBs, anti-HBc and/or HBV DNA)
• History of auto-immune diseases and/or use of immunosuppressive drugs
• History of HIV infection
• Known hypersensitivity to yeast of any vaccine constituent
• Donor with a history of HBV infection

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam Medical Centre

Amsterdam, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Engerix-B

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Erfan Nur, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erfan Nur, MD, PhD

CONTACT

0031-20-4442604; e.nur@amsterdamumc.nl

Management hematology

CONTACT

0031-20-4442604; hematology@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Principal Investigator

Model Details: Prospective observational cohort study. Six SCD patients per cohort will be vaccinated with a recombinant HBV vaccine before allogeneic MSD HSCT (cohort 1a) and haploidentical HSCT (cohort 1b). Six SCD patients not undergoing allogeneic HSCT will be vaccinated as controls (cohort 2). Six haploidentical donors and six matched sibling donors of unvaccinated receivers will be vaccinated against HBV before stem cell donation (cohort 3a and 3b, respectively). All vaccinated patients and the receivers of stem cells of vaccinated donors will receive a booster vaccination at 12 months post-transplantation. Follow-up will be until 2 years post-transplantation.

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: January 20, 2022
• Study Start: June 8, 2021
• Primary Completion: January 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 8, 2023

Record last verified: 2023-06

Locations

NL (1)