Trial Title:
Clinical Trial Assessing the Safety and Immunologic Correlates of Heterologous Prime-Boost With pNGVL4a-Sig/E7(Detox)/HSP70 and TA-HPV in Healthy Donors Followed by Peripheral Blood Collection
NCT ID:
NCT06508138
Condition:
HPV 16 Infection
HPV-Related Carcinoma
Recurrence
Metastatic Cancer
Conditions: Official terms:
Recurrence
Conditions: Keywords:
HPV
Papivax
Seiwert
non myeloablative allogeneic bone marrow transplant
alloBMT
HPV16
J21112
J2199
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Enrolling by invitation
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized to one of two groups:
Arm A: Donors on this arm of the study will donate cells and bone marrow to the paired
recipient (who will receive a standard allogeneic stem cell transplant, Cytoxan, and may
receive HPV-specific donor lymphocyte cell infusion (DLI) at Day 90, depending on the
donor's response).
Arm B: Donors on this arm of the study will donate cells to the donor's paired recipient
(who will receive Cytoxan followed by HPV-specific DLI).
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
pNGVL4a-Sig/E7(detox)/HSP70 plasmid DNA; TA-HPV vaccinia virus
Description:
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
Arm group label:
Blood Donation Only for Recipient's CD-8 Depleted DLI
Arm group label:
Blood and Bone Marrow Donation for Recipient Patient's alloBMT
Other name:
PVX1
Summary:
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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-menopausal as defined by absence of or missed menstruation after normal
menstrual cycle for ≥ 12 months;
2. Surgically sterile or have a partner who is sterile (i.e., vasectomy in males
or absence of ovaries and/or uterus in females);
3. Use of medically effective contraception with a failure rate of less than 1%
per year when used consistently and correctly from screening until 3 months
following last dose. (Acceptable methods include hormonal contraception
(including implants or combined oral + injected); two barrier methods (e.g.,
condom with spermicide and cervical cap); or abstinence when this is the
subject's preferred and usual lifestyle.
- 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:
- Prior vaccination with any HPV antigen (prophylactic or therapeutic) except L1.
Individuals who have been immunized with licensed prophylactic HPV vaccines (e.g.
Gardasil®, Cervarix®) are not excluded.
- Subjects who have had chemotherapy, radiation, biological cancer therapy, or other
investigational.
- Subjects who have had surgery within 28 days of dosing of investigational agent,
excluding minor procedures (dental work, skin biopsy, etc.).
- History of myocarditis or pericarditis, or other known underlying heart disease
(e.g., cardiomyopathy, congestive heart failure, symptomatic arrhythmia not
controlled by medication, unstable angina, history of acute myocardial infarction or
cerebrovascular accident within the past 6 months)
- Subjects with an uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection/sepsis, or psychiatric illness/social situations that
would limit compliance with study requirements.
- A history of current or recent concurrent malignancy (≤ 5 years) except nonmelanoma
skin cancer.
- Subjects with active or chronic infection of HIV, HCV, or HBV.
- Subjects who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic
lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis
(MS), ankylosing spondylitis) with immunodeficiency as a clinical component.
- Subjects treated with immunosuppressive drugs such as cyclosporine,
adrenocorticotropic hormone (ACTH), alkylating agents, antimetabolites, radiation,
Tumor Necrosis Factor (TNF) inhibitors, or systemic corticosteroids, either
chronically or in the past 2 months
- Subjects with a recognized immunodeficiency disease including cellular
immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have
acquired, hereditary, or congenital immunodeficiencies.
- Subjects and the subject's close social, sexual, or domestic contacts may not have
no-nhealed wounds or active exfoliative skin conditions such as: Eczema, Burns,
Impetigo, Varicella-zoster virus infection, Herpes simplex virus infection, Severe
acne, Severe diaper dermatitis with extensive areas of denuded skin, Psoriasis,
Lichen planus, Darier disease (keratosis follicularis)
- History or presence of atopic dermatitis
- Conditions associated with immunosuppression such as HIV/AIDS, leukemia, lymphoma,
generalized malignancy, solid organ transplant or hematopoietic stem cell transplant
recipients
- Active drug or alcohol use or dependence that, in the opinion of the investigator,
would interfere with adherence to study requirements or assessment of immunologic
endpoints.
- Prisoners or subjects who are compulsorily detained (involuntary incarceration) for
treatment of either a physical or psychiatric illness.
- Any illness or condition that in the opinion of the investigator may affect the
safety of the subject or the evaluation of any study endpoint.
- Women of child-bearing potential who are not on any form of birth control will be
excluded.
- Breast feeding
- No close social contact with children under 5 years old or close social or domestic
contact with a pregnant woman
- Serious vaccine component allergy
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Start date:
October 18, 2023
Completion date:
October 18, 2025
Lead sponsor:
Agency:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class:
Other
Collaborator:
Agency:
PapiVax Biotech, Inc.
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06508138
