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

• Status: Recruiting
• Trial end date: 2033-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; The Methodist Hospital Research Institute
• Treatments: Cyclophosphamide; Fludarabine; Nivolumab

Criteria

Inclusion Criteria:

PROCUREMENT

1. Diagnosis of a cancer for which the presence of a high risk HPV type has been documented in a biopsy sample

2. Cancer is:

• recurrent or persistent after standard therapy

• OR patient is unable to receive standard therapy

3. Karnofsky score ≥ 50%

4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

TREATMENT

1. Diagnosis of a cancer for which the presence of a high risk HPV type has been documented in a biopsy sample

2. Cancer is:

• recurrent or persistent after standard therapy

• OR patient is unable to receive standard therapy

3. Life expectancy ≥ 6 weeks.

4. Age ≥ 18 years.

5. Karnofsky score ≥ 50%

6. Bilirubin < 3 × upper limit of normal (ULN), AST < 5 × ULN, Hgb ≥ 7.0 g/dL

7. Pulse oximetry of > 90% on room air.

8. GFR > 30 mL/min calculated by the Cockcroft-Gault, MDRD study, or CKD-EPI creatinine equations, or equivalent

9. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

10. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

Exclusion Criteria:

PROCUREMENT

1. Known HIV positivity.

TREATMENT

1. Currently receiving any investigational agents or have received any tumor vaccines or T cell antibodies within previous 4 weeks.

2. Severe intercurrent infection.

3. Pregnancy or lactation.