Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated or Viral Neoantigens in a Patient With Metastatic Cancer Plus the Administration of Pembrolizumab

• Status: Withdrawn
• Trial end date: 2021-01-27
• Target enrollment: 0
• Participant gender: All

Summary

Background:

A cancer treatment has been developed called "gene transfer" or "gene therapy." It involves taking white blood cells from a person (called apheresis), genetically modifying the cells in a lab to recognize cancer, and then giving the cells back to the person. Researchers want to see if this treatment can help people with metastatic squamous cell anal cancer.

Objective:

To see if treating cancer with a person s own white blood cells that have been genetically modified can cause tumors to shrink.

Eligibility:

People who have metastatic squamous cell anal cancer for which standard treatments have not worked.

Design:

Participants will have had a tumor biopsy and apheresis to collect white blood cells under a separate protocol.

Participants will stay at the hospital for 3 to 4 weeks. They will have an intravenous (IV) catheter placed in a large vein in the upper chest.

Participants will get chemotherapy drugs (fludarabine and cyclophosphamide), the cell infusion, and aldesleukin through the IV. Pembrolizumab is given before and for three doses given every three weeks after the cell infusion. Aldesleukin will help the cells grow.

Participants will take an antibiotic, antiviral, and antifungal by mouth. They will get an injection of filgrastim. It will stimulate the formation of white blood cells.

Participants will have blood and urine tests. They will have physical exams. Their symptoms will be reviewed. They will have imaging scans.

About 6 and 12 weeks after they finish treatment, participants will have safety follow-up visits. These visits will take 1 to 2 days.

Participants will return to the Clinical Center every 3 to 6 months for 3 years, and then as determined by their doctor. They will be followed long term for up to 15 years on a separate study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Pembrolizumab

Criteria

-INCLUSION CRITERIA:

1. Measurable (per RECIST v1.1 criteria), metastatic squamous cell anal cancer.

2. Refractory to approved standard systemic therapy.

3. Clinical performance status of ECOG 0 or 1

4. Willing to practice birth control from the time of enrollment on this study and for four months after treatment.

5. Must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.

6. Serology

• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

• Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

7. Hematology

• ANC > 1000/mm^3 without the support of filgrastim

• WBC >= 3000/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin > 8.0 g/dL. Subject may be transfused to reach this cut-off.

8. Chemistry

• Serum ALT/AST <= 5.0 x ULN

• Serum creatinine <= 1.6 mg/dL

• Total bilirubin <= 2.0 mg/dL, except in patients with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL.

9. More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment. Note: Patient may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to grade 1 or less.

10. Ability of subject to understand and the willingness to sign a written informed consent document.

11. Willing to sign a Durable Power of Attorney Form.

12. Subject must be co-enrolled on protocol 03-C-0277.

EXCLUSION CRITERIA:

1. Patient is pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

2. Concurrent systemic steroid therapy.

3. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).

5. History of major organ autoimmune disease.

6. Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1, including but not limited to myocarditis and pneumonitis.

7. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptible to its toxicities.)

8. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.

9. History of coronary revascularization or ischemic symptoms.

10. Patient is known to have an LVEF <= 45%.

11. Patient is receiving any other investigational agents.