Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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…
Inclusion Criteria: * HLA-haploidentical relative of a patient with advanced HPV 16-associated malignancy * Female or male subjects age 18-70 years of age with a BMI ≥ 18.5 kg/m2. * Subjects must understand and agree to comply with the requirements of the study by signing an Informed Consent Form (ICF) indicating voluntary consent to participate in the study prior to the initiation of Screening or study-related activities. * Able and willing to comply with all study procedures. * Must meet at least one of the following three criteria with respect to reproductive capacity: 1. Post-menopausa…
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