Non-Viral TCR Gene Therapy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04102436|
Recruitment Status : Suspended ((suspension))
First Posted : September 25, 2019
Last Update Posted : October 20, 2021
A person s white blood cells can be modified in a lab to recognize certain changes in their tumor. Many of these cells are collected from the person, modified, then given back to the person. This may help treat some cancers.
To learn if a person s white blood cells modified with T-cell receptors can cause solid tumors to shrink.
People ages 18-70 who have cancer of the gastrointestinal tract, genitourinary tract, ovary, breast, or lung that has spread, or who have glioblastoma.
Participants will be screened and have their cells prepared for treatment in another protocol.
Participants will be hospitalized one week before treatment. They will stay approximately 3 - 4 weeks after treatment.
Participants will get the modified white blood cells and chemotherapy through an IV catheter, which is a small plastic tube inserted in a vein.
Participants will take drugs by mouth to prevent infection. They will receive filgrastim as a shot or injection under the skin.
Participants will have tests before, during, and after treatment:
Heart, blood, and urine tests
Scans: They will lie in a machine that takes pictures of the body.
Possible apheresis: The participant s blood is removed through a needle in an arm. The blood goes through a machine that removes the white blood cells. The rest of the blood is returned through a needle in the other arm.
Participants will have visits about 6 and 12 weeks after treatment. If they are responding to treatment, they will then have visits every 3-6 months for 3 years. Then they will join another study and be followed about 12 more years.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Non-Small Cell Lung Cancer Breast Cancer Gastrointestinal/Genitourinary Cancer Ovarian Cancer||Drug: Fludarabine Drug: Cyclophosphamide Drug: Aldesleukin Biological: Sleeping Beauty Transposed PBL||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||210 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Using the Administration of Autologous T-Cells Engineered Using the Sleeping Beauty Transposon/Transposase System to Express T-Cell Receptors Reactive Against Mutated Neoantigens in Patients With Metastatic Cancer|
|Estimated Study Start Date :||December 7, 2021|
|Estimated Primary Completion Date :||December 31, 2028|
|Estimated Study Completion Date :||December 31, 2029|
Experimental: 1/Experimental Therapy
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + Sleeping Beauty Transposed PBL + high- or low-dosealdesleukin.
Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
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.
Aldesleukin 720,000 IU/kg (based on total body weight) IV 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 be eligible to receive 72,000 IU/kg IV.
Biological: Sleeping Beauty Transposed PBL
Day 0: Cells are to be infused at a dose not to exceed 1.5e11 in 400 mL intravenously on the Patient Care Unit over 20-30 minutes or as clinically determined by an investigator for patient safety (between 2-4 days after the last dose of fludarabine).
- 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 ]Percentage of patients who have a clinical response to treatment (objective tumor regression)
- Phenotypic and functional characteristics of PBL [ Time Frame: 2-4 years post cell infusion ]Patient PBL will be obtained from whole blood and then evaluated for function and phenotype
- Safety and tolerance [ Time Frame: 6 weeks (+/- 2 weeks) following administration of the cell product ]Using standard CTCAE 5.0
- Immune monitoring [ Time Frame: 6 weeks (+/-2 weeks) following administration ofthe cell product ]Will consist of quantifying T- cells reactive with HLA- matched tumor cells using established techniques such as intracellular FACS, cytokine release assays, and ELISpot assays.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04102436
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|