RecruitingPhase 2NCT03412877

Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

A Phase II Study Using the Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in Patients With Metastatic Cancer


Sponsor

National Cancer Institute (NCI)

Enrollment

285 participants

Start Date

Sep 6, 2018

Study Type

INTERVENTIONAL

Conditions

Summary

Background: A person s tumor is studied for mutations. When cells are found that can attack the mutation in a person s tumor, the genes from those cells are studied to find the parts that make the attack possible. White blood cells are then taken from the person s body, and the gene transfer occurs in a laboratory. A type of virus is used to transfer the genes that make those white blood cells able to attack the mutation in the tumor. The gene transfer therapy is the return of those white blood cells back to the person. Objective: To see if gene transfer therapy of white blood cells can shrink tumors. Eligibility: People with certain metastatic cancer for which standard treatments have not worked. Design: Participants may complete screening under another protocol. Screening includes: * Getting tumor cells from a previous procedure * Medical history * Physical exam * Scans * Blood, urine, heart, and lung tests The study has 8 stages: 1. Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm. 2. Care at home over approximately 12 weeks. 3. Stopping therapy for 4-6 weeks while their cells are changed in a lab. 4. Hospital stay approximately 3-4 weeks for treatment. An IV catheter will be placed in the chest to administer drugs. 5. Patients on Arm 2 of the study will receive the first dose of pembrolizumab while in the hospital. Three additional doses will be given after the cell infusion 3 weeks apart. 6. Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer. 7. Recover in the hospital for 1-2 weeks. Participants will get drugs and have blood and urine tests. 8. Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined.


Eligibility

Min Age: 18 YearsMax Age: 72 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing a personalized immune cell therapy where your own immune cells are genetically modified in a lab to specifically recognize and attack the unique mutations in your cancer — essentially creating a custom treatment designed for your tumor. **You may be eligible if...** - You have metastatic (spread) solid cancer that can be measured on scans, in one of these categories: gastrointestinal or genitourinary cancers; breast, ovarian, or other solid cancers; non-small cell lung cancer; endocrine or neuroendocrine tumors; or multiple myeloma with measurable solid tumors - You have tried standard treatments and your cancer has progressed - You are in reasonably good health and able to perform basic daily activities - You are willing to undergo blood draws and biopsies for cell collection **You may NOT be eligible if...** - You have active autoimmune disease requiring treatment - You have had a prior stem cell transplant from a donor - You have serious heart, lung, liver, or kidney problems - You are pregnant or breastfeeding - You have active HIV, hepatitis B, or hepatitis C Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGCyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

DRUGFludarabine

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

DRUGAldesleukin

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 10 doses). Patients in Cohort 3 may receive 72,000 IU/kg IV.

BIOLOGICALIndividual Patient TCR-Transduced PBL

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

DRUGPembrolizumab (KEYTRUDA(R))

Arm 2: Pembrolizumab 2 mg/kg IV over approximately 30 minutes on Days -2, 21, 42, and 63.


Locations(1)

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

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NCT03412877


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