Transplant-Related Cancer
Conditions
Brief summary
This research is being done to understand the effects of certain types of bone marrow transplant (BMT) on the immune system. Your doctors are planning a BMT, using one of your family members as the bone marrow donor, for your cancer. Part of that BMT involves a chemotherapy drug, called Cyclophosphamide (Cytoxan), given after the transplant. This research is being done to understand the effects of Cyclophosphamide on the immune system.
Detailed description
The research will involve giving your donor a vaccine against a certain infection, before the bone marrow donation: either a vaccine against hepatitis (the hepatitis A vaccine), or a vaccine against pneumonia (Prevnar). You will then get both of these vaccines following your transplant. By studying how much these vaccines may improve your immune system, we hope to better understand the effects of the BMT with Cyclophosphamide on the immune cells. Prevnar is a pneumococcal vaccine (pneumococcus is a bacteria that can cause pneumonia and other infections). It is approved by the Food and Drug Administration (FDA) for the prevention of infections in children. It is not usually given to adults. Hepatitis A vaccine is approved by the FDA for the prevention of hepatitis A (a liver infection) in children and adults. The vaccines are not approved for bone marrow donors or for vaccinating adults after BMT (using these vaccines in this research is investigational). The FDA is allowing the use of these vaccines in this research study. Certain people getting BMT followed by Cyclophosphamide may join, if their donors might also join. Your bone marrow donor must take part in this study, in order for you to continue on this study
Interventions
BIOLOGICALHavrix
1440 ELISA units, or 1 mL, IM
BIOLOGICALPCV13
0.5 mL IM
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Only the study pharmacist was unblinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Patients inclusion for study: 1. Patient age \> 18 years. 2. Plan to undergo one of the following types of transplant, using bone marrow from a related donor: * Myeloablative, HLA matched or partially HLA-mismatched (haploidentical), related-donor bone marrow transplantation that includes high-dose posttransplantation Cy * 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. Patients inclusion for vaccine: 1. Receipt of the type of myeloablative or nonmyeloablative BMT 2. The bone marrow donor has received the pre-bone marrow harvest vaccine (either Prevnar or hepatitis A vaccine) on this study. Donors inclusion: 1\. Donor age \> 18 years.
Exclusion criteria
Patients exclusion for study entry: 1. Hypersensitivity to either the components of hepatitis A vaccine (including neomycin) or the components of the PCV7 and PCV13 vaccines (including diphtheria toxin). 2. Severe latex allergy. Patients exclusion for vaccine: 1. Graft failure. 2. 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. 3. Systemic immunosuppression for GVHD treatment or prophylaxis within 4 weeks (+/- 5 days) prior to vaccination. 4. Pregnant or breastfeeding Donors exclusion: 1. Hypersensitivity to both the components of hepatitis A vaccine (including neomycin) and the components of the PCV7 and PCV13 vaccines (including diphtheria toxin). 2. Severe latex allergy. 3. Expected to be on systemic immunosuppressants between the time of vaccination and the bone marrow donation. 4. Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T-cell Immunity Augmentation | up to 6 months | Number of participants in which patient-donor pairs were not pre-immune to hepatitis A or CRM197, show augmented T-cell immunity when the vaccine is also given to the bone marrow donor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recipient Vaccine-specific T-cell Response Post-transplant, Before Vaccination | up to 6 months | Number of participants with a greater T-cell response after receiving transplant from a donor who received a vaccine, before receiving post-transplant vaccination. |
| Recipient Vaccine-specific T-cell Response After Post-transplantation Vaccine | up to 6 months | Number of participants with a greater T-cell response after receiving transplant from a donor who received a vaccine, and after receiving post-transplant vaccination. |
Countries
United States
Participant flow
Pre-assignment details
8 recipients and 8 donors were screen failures prior to starting the study. 8 additional donors were vaccinated, but their intended recipients were never vaccinated and were replaced on study due to early relapse or graft failure. Data for the latter 8 donors has been lost and their arm assignment cannot be determined.
Participants by arm
| Arm | Count |
|---|---|
| Donor Vaccine Donors are randomized to receive either Havrix or PCV13 prior to bone marrow donation. | 52 |
| Recipient Vaccine Recipients receive Havrix and PCV13 post bone marrow transplant. | 52 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 2 | 0 |
| Overall Study | Graft failure | 0 | 0 | 3 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 11 | 0 |
| Overall Study | Relapse | 0 | 0 | 17 | 6 |
Baseline characteristics
| Characteristic | Recipient Vaccine | Total | Donor Vaccine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 10 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants | 94 Participants | 50 Participants |
| Age, Continuous | 54 years | 50 years | 41.5 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 52 Participants | 104 Participants | 52 Participants |
| Sex: Female, Male Female | 22 Participants | 43 Participants | 21 Participants |
| Sex: Female, Male Male | 30 Participants | 61 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 2 / 52 |
| other Total, other adverse events | 0 / 52 | 0 / 52 |
| serious Total, serious adverse events | 0 / 52 | 0 / 52 |
Outcome results
Primary
T-cell Immunity Augmentation
Number of participants in which patient-donor pairs were not pre-immune to hepatitis A or CRM197, show augmented T-cell immunity when the vaccine is also given to the bone marrow donor.
Time frame: up to 6 months
Population: Samples collected were inadequate for analysis, therefore data could not be collected to assess this outcome measure.
Secondary
Recipient Vaccine-specific T-cell Response After Post-transplantation Vaccine
Number of participants with a greater T-cell response after receiving transplant from a donor who received a vaccine, and after receiving post-transplant vaccination.
Time frame: up to 6 months
Population: Samples collected were inadequate for analysis, therefore data could not be collected to assess this outcome measure.
Secondary
Recipient Vaccine-specific T-cell Response Post-transplant, Before Vaccination
Number of participants with a greater T-cell response after receiving transplant from a donor who received a vaccine, before receiving post-transplant vaccination.
Time frame: up to 6 months
Population: Samples collected were inadequate for analysis, therefore data could not be collected to assess this outcome measure.