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About
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.
Full description
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.
Enrollment
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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:
Medically healthy with no clinically significant findings in the physical examination, medical history, vital signs.
Normal screening ECG or screening ECG with no clinically significant findings as judged by the Investigator.
No history of any clinically significant immunosuppressive or autoimmune disease including hematologic malignancy or history of solid organ or bone marrow transplantation
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
White blood cell count ≥ 3,000
Lymphocyte number ≥ 500
Absolute neutrophil count ≥ 1,000
Platelets ≥ 90,000
Hemoglobin ≥ 9
Total bilirubin < 1.5 x upper limit of normal (ULN) (< 3 x ULN if Gilbert's disease)
Cardiac Troponin < 0.04 ng/mL
AST(SGOT)/ALT(SGPT) < 3 x ULN
Creatinine < 1.5 x ULN or estimated creatinine
clearance ≥ 60 mL/min per Modified
Cockroft-Gault Formula
Exclusion criteria
Primary purpose
Allocation
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24 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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