Patient-donor Vaccination in the Context of Allogeneic Bone Marrow Transplant With Post-transplant Cyclophosphamide

Patient-donor Vaccination in the Context of Allogeneic Bone Marrow Transplant (BMT) With High-dose Post Transplantation Cyclophosphamide.

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.

Study Overview

• Status: Terminated
• Conditions: Transplant-Related Cancer
• Intervention / Treatment: Biological: PCV13; Biological: Havrix

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

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Donor PCV13; Donors receive PCV13 prior to bone marrow donation.	Biological: PCV13; 0.5 mL IM; Other Names: Prevnar-13
Active Comparator: Donor Havrix; Donors receive Havrix prior to bone marrow donation.	Biological: Havrix; 1440 ELISA units, or 1 mL, IM; Other Names: Hepatitis A vaccine
Active Comparator: Recipient vaccine; Recipients receive Havrix and PCV13 post bone marrow transplant.	Biological: PCV13; 0.5 mL IM; Other Names: Prevnar-13; Biological: Havrix; 1440 ELISA units, or 1 mL, IM; Other Names: Hepatitis A vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6 months
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.	up to 6 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: RIchard Ambinder, M.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 13, 2011
• First Submitted That Met QC Criteria: January 21, 2011
• First Posted (Estimate): January 24, 2011

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 8, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: J10140; P01CA015396 (U.S. NIH Grant/Contract); NA_00044665 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No