Acute Myeloid Leukaemia, Diffuse Large B Cell Lymphoma (DLBCL), HPV (Human Papillomavirus)-Associated, Myelodysplastic Syndrome, Recipients of Allogeneic Stem Cell Transplantation
Conditions
Brief summary
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.
Interventions
BIOLOGICALEarly 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.
BIOLOGICALLate 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.
Sponsors
Vastra Gotaland Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary outcome - GMT level against HPV 16 | Early group: at month 16 posttransplant. Late group: at month 22 posttransplant. | Antibody level (GMT - geometric mean titer) against HPV 16 measured 1 months after the third vaccine dose, early vs late. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcome 1 - GMT level against all 9 HPV-serotypes | Early group: at month 16 posttransplant. Late group: at month 22 posttransplant. | 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. |
| Secondary Outcome 2 - GMT level against all 9 HPV-serotypes | Early group: at month 27 posttransplant. Late group: at month 33 posttransplant. | 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. |
| Secondary Outcome 3 - Proportion seropositive/negative against 9 HPV-serotypes | Early group: at month 16 and month 27 posttransplant. Late group: at month 22 and month 33 posttransplant. | Proportion seropositive/negative against 9 HPV-serotypes included in vaccine measured 1 and 12 months after third dose. Early vs late. |
| Secondary Outcome 4 - Seroconversion against 9 HPV-serotypes | Early group: at month 16 posttransplant. Late group: at month 22 posttransplant. | Seroconversion against 9 HPV-serotypes included in vaccine, pre-vaccination compared to 1 month after third dose, early vs late. |
| Secondary Outcome 5 - Proportion seropositive against 7/9 HPV-types | Early group: at month 16 and month 27 posttransplant. Late group: at month 22 and month 33 posttransplant. | Proportion seropositive against 7/9 HPV-types included in the vaccine at 1 and 12 months after completion of vaccination. Early vs late. |
Countries
Sweden
Contacts
Primary ContactSigrun Einarsdottir, MD, PhD
Outcome results
None listed