HPV 16+ Recurrent or Metastatic CancerPhase 1/2NCT04713046
Safety and Efficacy of Allogeneic HPV-specific T Cells in Adults With Recurrent or Metastatic HPV16+ Cancers
A Phase 1/2 study testing CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16 and Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16 in people with HPV 16+ Recurrent or Metastatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
In this study, haploidentical relatives of a patient with recurrent or metastatic HPV 16-associated malignancy will be vaccinated with a therapeutic human papillomavirus (HPV) vaccine series to generate HPV-specific leukocytes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV 16+ Recurrent or Metastatic Cancer
- What is being tested?
- CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16 and Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Oct 2023to 1 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have pathologically confirmed incurable, locally recurrent or metastatic HPV16+ HNSCC
- Male or female ≥ 18 years of age
- Have an human leukocyte antigen (HLA) partially mismatched (haploidentical) related donor. Acceptable donors include first degree relatives (parent, child, or haploidentical sibling), half-siblings, or second degree relatives (aunt, uncle, cousin, niece, nephew). A patient who has inherited a recombinant haplotype from the parents is eligible if the donor shares at least 1 HLA antigen at each of the HLA-A, HLA-B, and HLA DR isotype (HLA-DR) loci.
- Prior treatment with a platinum-containing regimen
- Patients with an FDA-approved indication to receive an anti-programmed cell death protein-1 (PD-1) or anti-programmed death-ligand1 (PD-L1) monoclonal antibody must have received at least one cycle of this therapy prior to receiving treatment on this trial
- Life expectancy ≥ 4 months at time of screening
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- Measurable disease using RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been documented in such lesions
- Eastern Cooperative Oncology Group (ECOG) performance status of < 2 (see Appendix A).
- Adequate organ function per the protocol, as defined below:
- Left ventricular ejection fraction > 35% (within 30 days of eligibility screening)
- Total bilirubin < 3.0 mg/dl unless from Gilbert disease
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 4 x institutional upper limit of normal
- Serum creatinine < 3.0 mg/dl
- Willing and able to provide written informed consent
Who cannot join
- Disease that is suitable for local therapy administered with curative intent
- Requires vasopressor or ventilator support
- Received antithymocyte globulin or similar anti-T-cell antibody therapy ≤ 4 weeks prior to Cycle 1 Day 1
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy >10 mg/day of prednisone or equivalent, or any other form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1 of study treatment.
- Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Active infection requiring systemic therapy
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- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Received any live vaccine for up to 30 days prior to enrollment.
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer not associated with HPV16.
- Pregnancy or breastfeeding: females of childbearing potential must have a negative serum pregnancy test.
- Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception (abstinence is acceptable) for the course of the study through 120 days after the last study dose since the effects of this therapy on the developing human fetus are unknown.
- Inability to comply with study procedures
- Received chemotherapy or targeted small molecule therapy within 2 weeks of the first dose of cyclophosphamide. Subjects must have recovered (ie, grade ≤ 1 or at baseline) from adverse events (AEs) due to a previously administered agent. Subjects with grade ≤ 2 neuropathy or grade ≤ 2 alopecia are an exception to this criterion.
- Received prior radiotherapy within 2 weeks of the first dose of cyclophosphamide. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1- week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- Carcinomatous meningitis; and/or active CNS metastases, unless metastases are treated and stable and the subject does not require systemic steroids.
- Known history of human immunodeficiency virus (HIV), known active hepatitis B virus (HBV; e.g., hepatitis B surface antigen [HBsAg] reactive), or hepatitis C virus (HCV; e.g., HCV ribonucleic acid [RNA] is detected)
- Prior treatment with HPV T cells
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
About this study
Official title: A Phase I Clinical Trial Assessing the Safety, Feasibility and Immunologic Correlates of Allogeneic HPV-specific Cluster of Differentiation 4 (CD4)+ T Cells in Advanced HPV16-associated Malignancies
In this study, haploidentical relatives of a patient with recurrent or metastatic HPV 16-associated malignancy will be vaccinated with a therapeutic human papillomavirus (HPV) vaccine series to generate HPV-specific leukocytes. The cancer patient with recurrent or metastatic HPV16+ cancer will then be randomized to one of two arms: 1) non-myeloablative allogeneic bone marrow transplant or 2) cluster of differentiation 8 (CD8)-depleted donor lymphocyte infusion.
- Conditions
- HPV 16+ Recurrent or Metastatic Cancer
- Being tested
- CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16, Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16Biological
Patients will receive CD8+ T cell-depleted peripheral blood cells at one of three dose levels following cyclophosphamide: 1) 10^6 CD4+ cells/kg; 2) 5 x 10^6 CD4+ cells/kg; or 3) 10^7 CD4+ cells/kg of recipient ideal body weight.
Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16Biological
Standard dosing for bone marrow graft (target dose of 4 x 10^8 nucleated cells/kg) and if progression at Day 90, will receive dose level 1 for the CD8-depleted DLI (106 CD4+ cell/kg).
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic bone marrow transplant | Experimental | non-myeloablative allogeneic bone marrow transplant (BMT) from a haploidentical relative after vaccination with a therapeutic HPV vaccine series. Receives: Biological: Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16 |
| CD8-depleted donor lymphocyte infusion (DLI) per dose escalation scheme | Experimental | CD8-depleted donor lymphocyte infusion per dose escalation scheme from a haploidentical relative after vaccination with a therapeutic HPV vaccine series. Receives: Biological: CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Determine the safety of the two interventions in patients with recurrent or metastatic HPV16-associated cancer. Safety will be monitored for every patient and we will document and grade every adverse event using the NCI CTCAE version 5.0.
Measured: 12 months
Maximum Tolerated Dose (MTD) of Allogeneic CD4+ T cell Infusion
Determine the maximum tolerated dose (in CD4+ cells/kg) of allogeneic CD4+ T cells infused after cyclophosphamide in patients with recurrent or metastatic HPV16-associated cancer. We will use three dose levels of allogeneic CD4+ T cells: 1) 10^6 CD4+ cells/kg; 2) 5 x 10^6 CD4+ cells/kg; 3) 10^7 CD4+ cells/kg of recipient ideal body weight. We will implement a Bayesian optimal interval design to find the MTD with an observation period of 42 days for treatment-related toxicities.
Measured: 12 months
Secondary outcomes (5)
Number of toxicities as assessed by the NCI CTCAE version 5.0
Count the toxicities of allogeneic BMT and HPV-specific CD4+ T cells in patients with recurrent or metastatic HPV16-associated cancer. Toxicities of treatment will be formally assessed and scored using the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 12 months
Progression-free survival (PFS) of allogeneic CD4+ T cell Infusion and allogeneic BMT
PFS is defined as the date from transplantation to the date of relapse/progression, death from any cause or last follow-up, whichever comes first. Kaplan-Meier curve will be generated and PFS will be estimated along with 95% confidence intervals.
Measured: 12 months
Overall survival (OS) of allogeneic CD4+ T cell Infusion and allogeneic BMT
OS is defined as the date from infusion or transplantation to the date of death from any cause or last follow-up. A Kaplan-Meier curve will be generated along with 95% confidence intervals.
Measured: 12 months
Overall Response of allogeneic CD4+ T cell Infusion and allogeneic BMT
Response will be defined as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and will be evaluated at 2, 6 and 12 months after transplantation or infusion.
Measured: Up to 12 months
Incidence of acute graft versus host disease (GVHD)
Each patient will be monitored for acute GVHD and we will grade acute GVHD using the consensus conference clinical grading of acute GVHD.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2021
- Study start18 Oct 2023
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPV 16+ Recurrent or Metastatic CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized 1:1, 2-arm open-label trial
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- PapiVax Biotech, Inc.
- Responsible party
- Sponsor
- Investigators
- Philip Imus, MD, Principal investigator, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04713046
- Sponsor's protocol ID
- J21112
- Other IDs
- IRB00244082
- Status last verified
- Oct 2026
- First submitted
- 14 Jan 2021
- Last updated
- 28 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial Assessing the Safety, Feasibility and Immunologic Correlates of Allogeneic HPV-specific Cluster of Differentiation 4 (CD4)+ T Cells in Advanced HPV16-associated Malignancies
- ClinicalTrials.gov ID
- NCT04713046
- Acronym / sponsor ID
- J21112
- Conditions
- HPV 16+ Recurrent or Metastatic Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- PapiVax Biotech, Inc.
- Study start
- 18 Oct 2023 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 19 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, haploidentical relatives of a patient with recurrent or metastatic HPV 16-associated malignancy will be vaccinated with a therapeutic human papillomavirus (HPV) vaccine series to generate HPV-specific leukocytes. The cancer patient with recurrent or metastatic HPV16+ cancer will then be randomized to one of two arms: 1) non-myeloablative allogeneic bone marrow transplant or 2) cluster of differentiation 8 (CD8)-depleted donor lymphocyte infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized 1:1, 2-arm open-label trial
| Arm | Type | Receives |
|---|---|---|
| Allogeneic bone marrow transplant | Experimental | Biological: Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16non-myeloablative allogeneic bone marrow transplant (BMT) from a haploidentical relative after vaccination with a therapeutic HPV vaccine series. |
| CD8-depleted donor lymphocyte infusion (DLI) per dose escalation scheme | Experimental | Biological: CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16CD8-depleted donor lymphocyte infusion per dose escalation scheme from a haploidentical relative after vaccination with a therapeutic HPV vaccine series. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Have pathologically confirmed incurable, locally recurrent or metastatic HPV16+ HNSCC
- Male or female ≥ 18 years of age
- Have an human leukocyte antigen (HLA) partially mismatched (haploidentical) related donor. Acceptable donors include first degree relatives (parent, child, or haploidentical sibling), half-siblings, or second degree relatives (aunt, uncle, cousin, niece, nephew). A patient who has inherited a recombinant haplotype from the parents is eligible if the donor shares at least 1 HLA antigen at each of the HLA-A, HLA-B, and HLA DR isotype (HLA-DR) loci.
- Prior treatment with a platinum-containing regimen
- Patients with an FDA-approved indication to receive an anti-programmed cell death protein-1 (PD-1) or anti-programmed death-ligand1 (PD-L1) monoclonal antibody must have received at least one cycle of this therapy prior to receiving treatment on this trial
Key exclusion criteria (17 listed)
- Disease that is suitable for local therapy administered with curative intent
- Requires vasopressor or ventilator support
- Received antithymocyte globulin or similar anti-T-cell antibody therapy ≤ 4 weeks prior to Cycle 1 Day 1
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy >10 mg/day of prednisone or equivalent, or any other form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1 of study treatment.
- Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16Patients will receive CD8+ T cell-depleted peripheral blood cells at one of three dose levels following cyclophosphamide: 1) 10^6 CD4+ cells/kg; 2) 5 x 10^6 CD4+ cells/kg; or 3) 10^7 CD4+ cells/kg of recipient ideal body weight. | Biological | CD8-depleted donor lymphocyte infusion (DLI) per dose escalation scheme |
| Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16Standard dosing for bone marrow graft (target dose of 4 x 10^8 nucleated cells/kg) and if progression at Day 90, will receive dose level 1 for the CD8-depleted DLI (106 CD4+ cell/kg). | Biological | Allogeneic bone marrow transplant |
Primary outcome
Safety as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: 12 months
Determine the safety of the two interventions in patients with recurrent or metastatic HPV16-associated cancer. Safety will be monitored for every patient and we will document and grade every adverse event using the NCI CTCAE version 5.0.
Maximum Tolerated Dose (MTD) of Allogeneic CD4+ T cell Infusion
Time frame: 12 months
Determine the maximum tolerated dose (in CD4+ cells/kg) of allogeneic CD4+ T cells infused after cyclophosphamide in patients with recurrent or metastatic HPV16-associated cancer. We will use three dose levels of allogeneic CD4+ T cells: 1) 10^6 CD4+ cells/kg; 2) 5 x 10^6 CD4+ cells/kg; 3) 10^7 CD4+ cells/kg of recipient ideal body weight. We will implement a Bayesian optimal interval design to find the MTD with an observation period of 42 days for treatment-related toxicities.
5 secondary outcomes
Number of toxicities as assessed by the NCI CTCAE version 5.0
Time frame: 12 months
Progression-free survival (PFS) of allogeneic CD4+ T cell Infusion and allogeneic BMT
Time frame: 12 months
Overall survival (OS) of allogeneic CD4+ T cell Infusion and allogeneic BMT
Time frame: 12 months
Overall Response of allogeneic CD4+ T cell Infusion and allogeneic BMT
Time frame: Up to 12 months
Incidence of acute graft versus host disease (GVHD)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Imus, MD principal investigator
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CD8 reduced peripheral blood cells taken from related donors vaccinated against HPV16 and Non-myeloablative allogeneic bone marrow transplant from related donors vaccinated against HPV16 in people with HPV 16+ Recurrent or Metastatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.