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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

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.
• Cytoxan — DRUG
  500mg/m\^2/day x 3 days (on days -4, -3 and -2)
• Fludarabine — DRUG
  30mg/m\^2/day x 3 days (on days -4, -3, and -2)
• Nivolumab — BIOLOGICAL
  240mg every 2 weeks (+/- 3 days) starting on day -1

Study Details

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.

Key Dates

Start date

Sep 30, 2015

Status verified

Apr 2026

Primary completion

Jan 31, 2026

Completion

Jan 31, 2026

Study Design

Enrollment

32 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Group A
  HPV Specific T Cells
• Experimental: Group B
  HPV Specific T Cells plus lymphodepletion (Cytoxan and Fludarabine) and nivolumab

Primary Outcome Measure

Number of patients with dose limiting toxicity (DLT) [ Time Frame: 6 weeks ]

Locations (1)

Find similar trials in Houston, TX

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