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

NCT06508138 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 2 other identifiers: J2199IRB00243952
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HPV 16 Infection; HPV-Related Carcinoma; Recurrence; Metastatic Cancer

Keywords

HPV; Papivax; Seiwert; non myeloablative allogeneic bone marrow transplant; alloBMT; HPV16; J21112; J2199

Outcome Measures

Primary Outcomes (1)

• 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

  3 months

Study Arms (2)

Blood and Bone Marrow Donation for Recipient Patient's alloBMT

ACTIVE COMPARATOR

Donor patients receive the vaccination series. This will be followed by a bone marrow harvest under anesthesia that will be given to the donor's related recipient patient on the J21112 study. Then, depending on recipient response to allogeneic BMT, donor may return for collection of peripheral blood used to create CD8-depleted donor lymphocyte infusion (DLI) which will be given to the donor's related recipient patient on D90.

Biological: pNGVL4a-Sig/E7(detox)/HSP70 plasmid DNA; TA-HPV vaccinia virus

Blood Donation Only for Recipient's CD-8 Depleted DLI

ACTIVE COMPARATOR

Donor patients receive the vaccination series followed by collection of peripheral blood. This blood will be used to create the CD8-depleted donor lymphocyte infusion (DLI) which will be given to the donor's related recipient patient on the J21112 study.

Biological: pNGVL4a-Sig/E7(detox)/HSP70 plasmid DNA; TA-HPV vaccinia virus

Interventions

pNGVL4a-Sig/E7(detox)/HSP70 plasmid DNA; TA-HPV vaccinia virus BIOLOGICAL

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

Also known as: PVX1

Blood Donation Only for Recipient's CD-8 Depleted DLI; Blood and Bone Marrow Donation for Recipient Patient's alloBMT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Post-menopausal as defined by absence of or missed menstruation after normal menstrual cycle for ≥ 12 months;
• Surgically sterile or have a partner who is sterile (i.e., vasectomy in males or absence of ovaries and/or uterus in females);
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• PapiVax Biotech, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Neoplasms

Study Officials

• Philip Imus, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: July 18, 2024
• Study Start: October 18, 2023
• Primary Completion (Estimated): April 18, 2027
• Study Completion (Estimated): October 18, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)