This healthy related donor clinical trial is linked to a recipient clinical trial protocol for therapeutic purposes. In this healthy donor protocol, haploidentical relatives of a patient with recurrent or metastatic human papilloma virus (R/M HPV) 16-associated malignancy will be invited to be vaccinated with a therapeutic HPV vaccine series (PVX1) to generate HPV-specific white blood cells. In the linked recipient phase 1 clinical trial protocol, patient with incurable, locally recurrent or metastatic HPV 16-associated head and neck cancer will be randomized to one of two arms: Arm A: non-myeloablative (NMA) allogeneic bone marrow transplant (alloBMT) OR Arm B: CD8-depleted donor lymphocyte infusion (DLI) on Day 0 of a dose escalation scheme These two clinical trials are separated so that the healthy donor trial deals exclusively with issues of safety and immunological efficacy of the HPV vaccine series and this companion recipient trial examines the safety, feasibility and clinically efficacy of the allogeneic bone marrow graft and CD8-depleted DLI. The central hypothesis of the clinical trial is that patients with R/M HPV-associated malignancies can be safely and effectively treated by allogeneic bone marrow transplantation and/or CD8-depleted DLI from a healthy related donor that has been vaccinated against HPV16 E6 and E7 proteins.
Scientists have found that a family of viruses called the Human Papillomavirus (HPV) can cause certain cancers, particularly in the head and neck and cervix. Most of these cancers are caused by a specific type of HPV called HPV16. This research is being done to see if giving an investigational vaccine against HPV causes the participant's immune system to respond against proteins that are made by the vaccine and by the cancer in the participant's relative. The investigators would like to see if cells of the immune system that have responded to the vaccine can be found in the participant's blood. In a separate study the investigators will test if the blood and immune cells from the participant's blood can be given safely to the participant's relative and if the participant's cells cause the cancer in the participant's relative to shrink. The first two shots the participant would be given are a vaccine called "pNGVL4a-Sig/E7 (detox)/HSP70", and it contains DNA, the blueprint for making proteins. This vaccine is given as a shot into a muscle either in the shoulder or in the thigh. This will be followed by a third shot called "TA-HPV" which contains a vaccinia virus that helps the first shot to work by creating the T cells needed to fight cancer. After receiving the vaccines, the study team will collect the participant's immune system cells to give to the participant's relative with cancer. The collection will either be by bone marrow harvest or collection of the participant's circulating blood, depending on the group to which the participant and the participant's relative are randomized after enrolling in the trial. The use of this heterogeneous vaccination strategy in this research study is investigational, which means that the vaccine regimen is not approved for marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of the vaccine regimen in this study. Based on prior clinical studies, it is expected that this vaccine regimen and routes of administration will be well tolerated. In this research the investigators will also be collecting blood samples that may also be used in the future by researchers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
24
About 1 month before donating blood, donors are required to come to outpatient clinic once a week to receive the following vaccine series: Week 1: PVX1 (1 of 3): intramuscular injection (IM) of 3mg DNA prime with pNGVL4a-Sig/E7(detox)/HSP70 vaccine Week 2: PVX1 (2 of 3): IM 3mg DNA prime with pNGVL4a-Sig/E7(detox)/HSP70 vaccine Week 3: PVX1 (3 of 3): IM TA-HPV vaccinia boost Pause for 2 weeks Peripheral blood collection and possible bone marrow harvest depending on randomization
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Safety of Vaccine series as assessed by number of adverse events
Safety of the vaccine series will be assessed by counting number of adverse events
Time frame: 3 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.