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Preservation and Transfer of HBV Immunity After Allogeneic HSCT for SCD. (PROTECT)

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ClinicalTrials.gov Identifier: NCT05200338
Recruitment Status : Recruiting
First Posted : January 20, 2022
Last Update Posted : January 20, 2022
Sponsor:
Information provided by (Responsible Party):
Erfan Nur, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:

We hypothesize, that sickle cell disease (SCD) patients ending with mixed mononuclear chimerism after non-myeloablative HSCT with alemtuzumab/TBI conditioning will preserve their immune response to vaccinations administered prior to the transplantation and will therefore not need to be revaccinated. Furthermore, we hypothesize, that SCD patients after haploidentical HSCT can benefit from adoptive transfer of immunity from their donors.

To test the first hypothesis, we will vaccinate patients undergoing the alemtuzumab/TBI HSCT with a hepatitis B virus (HBV) vaccine before the transplant. To test the second hypothesis, we will vaccinate haploidentical and matched related donors 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, we will be able to evaluate whether SCD patients preserve their pre-transplant immune response in the post-transplantation period. Furthermore, we will determine whether donors transfer their immunity to HSCT recipients with SCD disease.


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Engerix-B Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Preservation and Transfer of Hepatitis B Virus Immunity After Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease Patients (Protect Study).
Actual Study Start Date : June 8, 2021
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Cohort 1a
SCD patients that are vaccinated against hepatitis B virus before matched sibling donor allogeneic SCT.
Drug: Engerix-B
Subjects are vaccinated with an accelerated scheme at 0, +1, +2 months with a booster at +12 months.

Cohort 1b
SCD patients that are vaccinated against hepatitis B virus before haploidentical donor allogeneic SCT.
Drug: Engerix-B
Subjects are vaccinated with an accelerated scheme at 0, +1, +2 months with a booster at +12 months.

Cohort 2
SCD patients that are vaccinated against hepatitis B virus without undergoing allogeneic SCT (control group).
Drug: Engerix-B
Subjects are vaccinated with an accelerated scheme at 0, +1, +2 months with a booster at +12 months.

Cohort 3a
SCD patients undergoing matched sibling donor allogeneic SCT whose donor is vaccinated against hepatitis B virus before stem cell collection.
Drug: Engerix-B
Subjects are vaccinated with an accelerated scheme at 0, +1, +2 months with a booster at +12 months.

Cohort 3b
SCD patients undergoing haploidentical donor allogeneic SCT whose donor is vaccinated against hepatitis B virus before stem cell collection.
Drug: Engerix-B
Subjects are vaccinated with an accelerated scheme at 0, +1, +2 months with a booster at +12 months.




Primary Outcome Measures :
  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. [ Time Frame: +1 year post-transplantation ]
    An antibody titer (anti-HBsAg) of >10IU/l is considered protective.


Secondary Outcome Measures :
  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 3-, 6-, and 24 months post-transplantation as compared to SCD patients without HSCT. [ Time Frame: 3-, 6-, and 24 months post-transplantation ]
  2. 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. [ Time Frame: 3-, 6-, 12- and 24 months post-transplantation ]
  3. 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). [ Time Frame: 3-, 6-, 12- and 24 months post-transplantation ]
  4. 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 [ Time Frame: 3-, 6-, 12- and 24-months post-transplantation ]


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Ages Eligible for Study:   16 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05200338


Contacts
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Contact: Erfan Nur, MD, PhD 0031-20-4442604 e.nur@amsterdamumc.nl
Contact: Management hematology 0031-20-4442604 hematology@amsterdamumc.nl

Locations
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Netherlands
Amsterdam Medical Centre Recruiting
Amsterdam, Netherlands, 1105AZ
Contact: Erfan Nur, MD, PhD    0031-20-4442604    e.nur@amsterdamumc.nl   
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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Principal Investigator: Erfan Nur, MD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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Responsible Party: Erfan Nur, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT05200338    
Other Study ID Numbers: METC 2021_091
First Posted: January 20, 2022    Key Record Dates
Last Update Posted: January 20, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Erfan Nur, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Sickle Cell Disease
Allogeneic stem cell transplantation
Mixed chimerism
Preservation of immunity
Adoptive transfer of immunity
Hepatitis B virus vaccination
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn