Vaccination Against Human Papillomavirus (HPV) After Allogeneic Stem Cell Transplantation

Vaccination Against Human Papillomavirus (HPV) in Women and Men After Stem Cell Transplantation

Patients who undergo allogeneic stem cell transplantation lose previously acquired immunity and are routinely revaccinated against many infectious diseases. For several reasons, these patients have a long-term immune deficiency due to the transplant itself (lack of immune reconstitution) and due to possible complications, primarily GvHD and its treatment. The risk of secondary malignancy in the long-term following an allogeneic bone marrow transplant is greatly increased, and secondary cancer cases account for a significant proportion of late deaths in both women and men after transplantation. Some of these secondary cancers are associated with HPV. The risk of cervical cancer has been reported to be 13 times increased compared to a healthy population.

Therefore in this trial, the aim is to study immune response (antigen-specific antibody response) after vaccination with 9-valent HPV vaccine (Gardasil 9®) in adult women and men (up to and including 45 years of age) who have undergone allogeneic stem cell transplantation. In this trial, the sponsor will compare "early" (start 9 months after tx) with "late" (start 15 months after tx) vaccination.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukaemia; Diffuse Large B Cell Lymphoma (DLBCL); HPV (Human Papillomavirus)-Associated; Recipients of Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Biological: Late post-transplant vaccination with Gardasil 9®; Biological: Early start post-transplant vaccination with Gardasil 9®

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

Contacts and Locations

• Study Contact: Name: Sigrun Einarsdottir, MD, PhD; Phone Number: 0046313427358; Email: sigrun.einarsdottir@vgregion.se

Study Locations

• Sweden
  • Region Skåne
    • Lund, Region Skåne, Sweden, 22242
      • Not yet recruiting
      • Skåne's University Hospital
      • Contact: Stina Wichert, MD; Phone Number: 004646-17 10 00; Email: Stina.Wichert@skane.se
      • Principal Investigator: Stina Wichert, MD
  • Region Stockholm
    • Stockholm, Region Stockholm, Sweden, 17176
      • Not yet recruiting
      • Karolinska University Hospital
      • Contact: Anna Nordlander, MD; Phone Number: 00468-123 700 00; Email: anna.nordlander@regionstockholm.se
      • Principal Investigator: Anna Nordlander, MD
  • Region Uppsala
    • Uppsala, Region Uppsala, Sweden, 75185
      • Recruiting
      • Uppsala University Hospital
      • Contact: Tobias Tolf, MD; Phone Number: 004618-611 00 00; Email: tobias.tolf@akademiska.se
      • Principal Investigator: Tobias Tolf, MD
  • Region Östergötaland
    • Linköping, Region Östergötaland, Sweden, 58185
      • Recruiting
      • Linköping University Hospital
      • Contact: Thomas Erger, MD; Phone Number: 004610-103 00 00; Email: Thomas.Erger@regionostergotland.se
      • Principal Investigator: Thomas Erger, MD
  • Västra Götalands Region
    • Gothenburg, Västra Götalands Region, Sweden, 41345
      • Recruiting
      • Sahlgrenska University Hospital
      • Contact: Sigrun Einarsdottir, MD, PhD; Phone Number: 0046313427358; Email: sigrun.einarsdottir@vgregion.se
      • Principal Investigator: Sigrun Einarsdottir, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Recipient of AlloSCT from related or unrelated donor.
• Adults (men and women) ≥18 years up to and including 45 years of age for vaccination.
• Patients can be included regardless of prior HPV vaccination prior to transplantation

Exclusion Criteria:

• Severe thrombocytopenia (under 50 x 10^9) not allowing intramuscular injection
• Severe acute GvHD grade III-IV.
• Extensive chronic GvHD requiring treatment with prednisone doses above 0.7 mg/kg/day plus at least two other systemic treatments against GvHD (for example ruxolitinib or photopheresis).
• Prednisone doses above 1mg/kg/day at study start.
• Treatment with rituximab 6 months before start of vaccination. Doses given later (unusual) do not require exclusion.
• Treatment within 3 months before start of vaccination with iv or sc immunoglobulin.
• Pregnancy, pregnancy desire or active pregnancy planning during time vaccine is given and up to three months after last vaccine dose.
• Treatment with blood thinning medication contraindicating intramuscular injection
• Allergy against Gardasil 9

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Late vaccination group; Subjects will receive Gardasil 9® as part of the late post-transplant vaccination, starting at 15 months after stem cell transplantation.	Biological: Late post-transplant vaccination with Gardasil 9®; Subjects will receive Gardasil 9® as part of the late post-transplant vaccination, starting at 15 months after stem cell transplantation.
Experimental: Early vaccination group; Subjects will receive Gardasil 9® as part of the early post-transplant vaccination, starting at 9 months after stem cell transplantation.	Biological: Early start post-transplant vaccination with Gardasil 9®; Subjects will receive Gardasil 9® as part of the early post-transplant vaccination, starting at 9 months after transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome - GMT level against HPV 16	Antibody level (GMT - geometric mean titer) against HPV 16 measured 1 months after the third vaccine dose, early vs late.	Early group: at month 16 posttransplant. Late group: at month 22 posttransplant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome 2 - GMT level against all 9 HPV-serotypes	Antibody level (GMT - geometric mean titer) against all 9 HPV-serotypes included in vaccine (-6, -11, -16, -18, -31, -33, -45, -52, -58) measured at 12 months after the third vaccine dose. Early vs late.	Early group: at month 27 posttransplant. Late group: at month 33 posttransplant.
Secondary Outcome 3 - Proportion seropositive/negative against 9 HPV-serotypes	Proportion seropositive/negative against 9 HPV-serotypes included in vaccine measured 1 and 12 months after third dose. Early vs late.	Early group: at month 16 and month 27 posttransplant. Late group: at month 22 and month 33 posttransplant.
Secondary Outcome 5 - Proportion seropositive against 7/9 HPV-types	Proportion seropositive against 7/9 HPV-types included in the vaccine at 1 and 12 months after completion of vaccination. Early vs late.	Early group: at month 16 and month 27 posttransplant. Late group: at month 22 and month 33 posttransplant.
Secondary outcome 1 - GMT level against all 9 HPV-serotypes	Antibody level (GMT - geometric mean titer) against all 9 HPV-serotypes included in vaccine (-6, -11, -16, -18, -31, -33, -45, -52, -58) measured 1 month after the third vaccine dose. Early vs late.	Early group: at month 16 posttransplant. Late group: at month 22 posttransplant.
Secondary Outcome 4 - Seroconversion against 9 HPV-serotypes	Seroconversion against 9 HPV-serotypes included in vaccine, pre-vaccination compared to 1 month after third dose, early vs late.	Early group: at month 16 posttransplant. Late group: at month 22 posttransplant.

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2025
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 24, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Bone Marrow Diseases; Lymphoma, Large B-Cell, Diffuse; Myelodysplastic Syndromes
• Other Study ID Numbers: ALLO-HPV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) from this clinical trial will not be publicly shared to protect participant privacy and confidentiality. However, researchers may contact the Principal Investigator to request access to de-identified data.

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