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

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT03412877
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 72 Years
Healthy Volunteers
Not accepted

Interventions

  • Cyclophosphamide — DRUG
    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.
  • Fludarabine — DRUG
    Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
  • Aldesleukin — DRUG
    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.
  • Individual Patient TCR-Transduced PBL — BIOLOGICAL
    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).
  • Pembrolizumab (KEYTRUDA(R)) — DRUG
    Arm 2: Pembrolizumab 2 mg/kg IV over approximately 30 minutes on Days -2, 21, 42, and 63.

Study Details

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.

Key Dates

Start date
Sep 6, 2018
Status verified
May 2026
Primary completion
Mar 23, 2027
Completion
Mar 23, 2028

Study Design

Enrollment
285 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 1/iTCR
    Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Individual Patient TCR-Transduced PBL + high- or low-dose aldesleukin
  • Experimental: 2/iTCR + Pembro
    Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Individual Patient TCRTransduced PBL + high- or low-dose aldesleukin + pembrolizumab prior to cell administration and 3 additional doses every 3 weeksfollowing cell infusion

Primary Outcome Measure

Response rate [ Time Frame: 6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2 years, then per PI discretion ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center
[email protected]
866-820-4505

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By specialty
OncologyBreast oncologyWomen's healthBlood cancerLung oncologyLung diseaseGynecologic oncology
By research site
National Institutes of Health Clinical Center· Bethesda, MD

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