HPV-16/18 E6/E7-Specific T Lymphocytes, Relapsed HPV-Associated Cancers, HESTIA

NCT02379520 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: H-36021 HESTIA
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Subjects have a type of cancer that has been associated with an infection with a virus called human papilloma virus (HPV). The cancer has come back, has not gone away after standard treatment or the subject cannot receive standard treatment. This is a research study using special immune system cells called HPVST cells, a new experimental treatment. Investigators want to find out if they can use this type of treatment in patients with HPV-cancers. They have discovered a way to grow large number of HPV-specific T cells from the blood of patients with HPV-cancers. They want to see if these special white blood cells, called HPVST cells, that will have been trained to kill HPV infected cells can survive in the blood and affect the tumor. They will also see if they can make the T cells more active against the HPV-cancers by engineering them to be resistant to the TGF-beta chemical that these HPV-cancers produce. They will grow these HPVST cells from the patient's blood. The purpose of this study is to find the biggest dose of HPVSTs that is safe, to see how long they last in the body, to learn what the side effects are and to see if the HPVSTs will help people with HPV associated cancers. If the treatment with HPVST cells alone proves safe (Group A), additional group of patients (Group B) will receive Nivolumab in addition to HPVST cells in a lymphodepleted environment. Nivolumab is an antibody therapy that helps T cells control the tumor and it is FDA approved for the treatment of certain types of cancers, including Hodgkin's lymphoma. Lymphodepletion will decrease the level of circulating T cells prior to infusion of HPVST cells, thereby giving them room to expand. The purpose of this part of the study is to find out if TGF-beta resistant HPVST cells in combination with Nivolumab are safe, how long they last in the body and if they are more effective than HPVST cells alone in controlling the tumor.

Conditions

Human Papillomavirus-Related Carcinoma; Human Papillomavirus Positive Oropharyngeal Carcinoma; Human Papillomavirus Positive Cervical Carcinoma; Human Papillomavirus Positive Anal Carcinoma; Human Papillomavirus Positive Vulvar Carcinoma; Human Papillomavirus Positive Penile Carcinoma

Keywords

recurrent cancer; refractory cancer; virus specific T-cells; gene therapy; HPV

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity (DLT)

  DLT will be defined as any toxicity that is irreversible or life threatening, defined as the following, considered to be possibly, probably, or definitely related to the HPVST injection. 1. Non-hematologic DLT is any grade 3 or grade 4 non-hematologic toxicity. 2. Hematologic DLT is defined as any grade 4 hematologic toxicity.

  6 weeks

Secondary Outcomes (1)

• Overall response rate

  6 weeks

Study Arms (2)

Group A

EXPERIMENTAL

HPV Specific T Cells

Genetic: HPV Specific T Cells

Group B

EXPERIMENTAL

HPV Specific T Cells plus lymphodepletion (Cytoxan and Fludarabine) and nivolumab

Genetic: HPV Specific T Cells; Drug: Cytoxan; Drug: Fludarabine; Biological: Nivolumab

Interventions

HPV Specific T Cells GENETIC

Dose escalation study with 5 dose levels: DL1-1×10\^7 cells/m2, DL2-3×10\^7 cells/m2, and DL3-1×10\^8 cells/m2, DL4- 2 to 3×10\^8 cells/m2, DL5- 0.8 to 1×10\^9 cells/m2 Group A -HPVST cells Group B -lymphodepletion \& nivolumab \& HPVST cells. First, treatment in Group A will be completed for DL1 and DL2. Only if DL2 in Group A proves safe, Group B will be treated on DL2, DL3, DL4, and DL5. Group A will be treated at DL3, DL4, and DL5 only if there is excessive toxicity in cohorts treated with lymphodepletion. HPVSTs will be given by IV injection over 1-10 minutes through a peripheral or a central line on day 0. If patients have clinical benefit (as determined by symptoms, physical exam or radiological studies) \& no significant toxicities, they may get up to 5 repeat infusions (for max total of 6 infusions) of HPVSTs at or below the same dose level.

Also known as: HPVSTs

Group A; Group B

Cytoxan DRUG

500mg/m\^2/day x 3 days (on days -4, -3 and -2)

Also known as: cyclophosphamide

Group B

Fludarabine DRUG

30mg/m\^2/day x 3 days (on days -4, -3, and -2)

Also known as: Fludara

Group B

Nivolumab BIOLOGICAL

240mg every 2 weeks (+/- 3 days) starting on day -1

Also known as: Opdivo

Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PROCUREMENT
• Diagnosis of a cancer for which the presence of a high risk HPV type has been documented in a biopsy sample
• Cancer is:
• recurrent or persistent after standard therapy
• OR patient is unable to receive standard therapy
• Karnofsky score ≥ 50%
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
• TREATMENT
• Diagnosis of a cancer for which the presence of a high risk HPV type has been documented in a biopsy sample
• Cancer is:
• recurrent or persistent after standard therapy
• OR patient is unable to receive standard therapy
• Life expectancy ≥ 6 weeks.
• Age ≥ 18 years.
• Karnofsky score ≥ 50%

You may not qualify if:

• PROCUREMENT
• \. Known HIV positivity.
• TREATMENT
• Currently receiving any investigational agents or have received any tumor vaccines or T cell antibodies within previous 4 weeks.
• Severe intercurrent infection.
• Pregnancy or lactation.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Recurrence; Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Carlos Ramos, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 25, 2015
• First Posted: March 5, 2015
• Study Start: September 1, 2015
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)