Patient-donor vaccination in the context of allogeneic BMT incorporating high-dose posttransplantation cyclophosphamide
Primary objective: In patient-donor pairs who are not pre-immune to hepatitis A or CRM, through this vaccination strategy determine whether the vaccine-specific T cell immunity observed in the patient is augmented when the vaccine is also given to the bone marrow donor. Secondary objectives 1.Determine if the recipient vaccine-specific T cell response after transplantation, immediately before vaccination, is greater when the vaccine is also given to the donor. 2.Determine if the recipient vaccine-specific T cell response after posttransplantation vaccination is greater when the vaccine is also given to the donor. 3.Similarly characterize vaccine-specific antibody titers in the transplant recipient. 4.Descriptively compare vaccine responses in donor-recipient pairs with preexisting immunity to hepatitis A or antigens present in PCV.
Patient eligibility for study entry 1.Patient age greater than 18 years. 2.Plan to undergo one of the following types of transplant, using bone marrow from a related donor: a.Myeloablative, matched related-donor bone marrow transplantation with high-dose posttransplantation Cy as the sole agent for GVHD prophylaxis b.Nonmyeloablative, HLA matched or partially HLA-mismatched, related-donor bone marrow transplantation that includes high-dose posttransplantation Cy Note: Patients who receive posttransplantation rituximab are eligible. 3.No known hypersensitivity to either the components of hepatitis A vaccine (including neomycin) or the components of the PCV7 and PCV13 vaccines (including diphtheria toxin). Note: Individuals with latex sensitivity are potentially eligible, but must notify the research staff of this sensitivity as latex-free vaccine is available. Patient eligibility for vaccination 1.Receipt of the type of myeloablative or nonmyeloablative BMT specified above (section 3.1). 2.The bone marrow donor has received the pre-bone marrow harvest vaccine (either Prevnar or hepatitis A vaccine) on this study. 3.No documented graft failure. 4.No documented disease progression or relapse, or disease persistence requiring treatment. Note: Patients with asymptomatic or low-volume disease progression or relapse may be eligible, determined on a case-by-case basis by the PI. 5.Off systemic immunosuppression for GVHD treatment or prophylaxis for at least 4 weeks prior to vaccination. 6.Not known to be pregnant or breastfeeding. Donor eligibility 1.Donor age greater than 18 years. 2.No known hypersensitivity to either the components of hepatitis A vaccine (including neomycin) or the components of the PCV7 and PCV13 vaccines (including diphtheria toxin). Note: Individuals with latex sensitivity are potentially eligible, but must notify the research staff of this sensitivity as latex-free vaccine is available. 3.Not expected to be on systemic immunosuppressants between the time of vaccination and the bone marrow donation. 4.Not known to be pregnant or breastfeeding.
TREATMENT PLAN 5.1 Donor vaccination 5.11 Donor history Baseline information on the donor (or anticipated donor) will include: â?¢history of hepatitis A infection and vaccination, if known â?¢history of pneumococcal infection and vaccination, if known â?¢adverse reactions to these vaccines â?¢use of systemic immunosuppressants History may be confirmed by obtaining relevant medical records and/or contact with a health care provider(s). 5.12 Type of vaccination Donors will be randomly assigned to be vaccinated once prior to bone marrow donation with either inactivated hepatitis A vaccine (Havrix; 1440 ELISA units, or 1 mL, IM), or PCV13 (0.5 mL IM). Individuals will receive the assigned vaccine regardless of immune status to that pathogen. If PCV13 is unavailable, PCV7 (0.5 mL IM) can be substituted. The study PI, co-PIâ??s, and laboratory personnel will be blinded to the vaccine assignment. The donor, designated study nurse, and investigational drug pharmacists will be unblinded. In the event that a potential donor is vaccinated and the paired transplant recipient does not complete the study, the donorâ??s slot in the randomization schedule will be replaced. 5.13Timing of vaccination Donors will be vaccinated a minimum of 10 days before donation, with a target at least 14 days. In the event that donors are vaccinated and the transplant then postponed, donors will not be revaccinated. The maximum desirable window between vaccination and bone marrow donation is 2 months. For a greater than 2 month interval, decision to remain on study will be made by the PI or co-PI. 5.2Patient vaccination 5.21Patient history Baseline information on the patient will include: â?¢history of hepatitis A infection and vaccination, if known â?¢history of pneumococcal infection and vaccination, if known â?¢adverse reactions to these vaccines In transplant recipients, use and type of posttransplantation immunosuppressants (e.g., systemic steroids, mycophenolate mofetil, calcineurin inhibitors, sirolimus, extracorporeal photopheresis) and GVHD history (onset, type, maximum grade) will be recorded for the following time frames: â?¢Between day 0 and vaccination (record type of immunosuppression and date range) â?¢Between vaccination and the post-vaccine research blood draw (section 7.0) Information may be confirmed by obtaining relevant medical records and/or contact with a health care provider(s). 5.22Type and timing of vaccination Following transplantation, patients will be vaccinated once with both inactivated hepatitis A vaccine (Havrix; 1440 ELISA units, or 1 mL, IM) and PCV13 (0.5 mL IM). If PCV13 is unavailable, PCV7 (0.5 mL IM) can be substituted. The vaccines will be administered on the same day. For myeloablative transplants (which use posttransplantation Cy alone for GVHD and graft rejection prophylaxis): â?¢Vaccinate on Day 90 (+/- 5 days), if patient has not been on systemic immunosuppression, or â?¢Vaccinate 4 weeks (+/- 5 days) after cessation of immunosuppression, no earlier than Day 90 (+/- 5 days) For nonmyeloablative transplants (which use posttransplantation Cy in combination with other immunosuppressants): â?¢Vaccinate 4 weeks (+/- 5 days) after cessation of immunosuppression Thus patients who develop GVHD requiring systemic immunosuppression before the vaccines are due, would have the pre-vaccine research blood and vaccines postponed until 4 weeks (+/- 5 days) after cessation of the immunosuppression. Vaccination may be postponed based on clinical status. 5.3Research samples The schedule for donor and patient research samples is provided in Section 7.0. 5.4Supportive care Supportive care will be delivered according to institutional guidelines and good medical practice
09/20/2014 04:03 AM