Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT06253520 |
Recruitment Status :
Recruiting
First Posted : February 12, 2024
Last Update Posted : May 17, 2024
|
Tracking Information | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | February 9, 2024 | ||||||||||||||
First Posted Date ICMJE | February 12, 2024 | ||||||||||||||
Last Update Posted Date | May 17, 2024 | ||||||||||||||
Estimated Study Start Date ICMJE | May 23, 2024 | ||||||||||||||
Estimated Primary Completion Date | June 15, 2031 (Final data collection date for primary outcome measure) | ||||||||||||||
Current Primary Outcome Measures ICMJE |
|
||||||||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||||
Change History | |||||||||||||||
Current Secondary Outcome Measures ICMJE |
Safety [ Time Frame: From study treatment initiation up to 4 weeks after the last study treatment ] The number of participants with toxicity of grade 3 or higher related to the KRAS-TCR transduced cells or vaccine, according to type of toxicity. Adverse events assessed per CTCAE version 5.
|
||||||||||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Descriptive Information | |||||||||||||||
Brief Title ICMJE | Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer | ||||||||||||||
Official Title ICMJE | A Phase Ib Clinical Trial to Evaluate the Administration of Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer | ||||||||||||||
Brief Summary | Background: Many cancer cells produce substances called antigens that are unique to each cancer. These antigens stimulate the body s immune responses. One approach to treating these cancers is to take disease-fighting white blood cells from a person, change those cells so they will target the specific proteins (called antigens) from the cancer cells, and return them to that person s blood. The use of the white blood cells in this manner is one form of gene therapy. A vaccine may help these modified white cells work better. Objective: To test a cancer treatment that uses a person s own modified white blood cells along with a vaccine that targets a specific protein. Eligibility: Adults aged 18 to 72 years with certain solid tumors that have spread after treatment. Design: Participants will undergo leukapheresis: Blood is removed from the body through a tube attached to a needle inserted into a vein. The blood passes through a machine that separates out the white blood cells. The remaining blood is returned to the body through a second needle. Participants will stay in the hospital for 3 or 4 weeks. They will take chemotherapy drugs for 1 week to prepare for the treatment. Then their modified white cells will be infused through a needle in the arm. They will take other drugs to prevent infections after the infusion. The vaccine is injected into a muscle; participants will receive their first dose of the vaccine on the same day as their cell infusion. Participants will have follow-up visits 4, 8, and 12 weeks after the cell infusions. They will receive 2 or 3 additional doses of the boost vaccine during these visits. Follow-up will continue for 5 years, but participants will need to stay in touch with the gene therapy team for 15 years. ... |
||||||||||||||
Detailed Description | Background:
Objectives: -Primary objective: --Determine the safety and efficacy of administering autologous T cells transduced to express receptors targeting KRAS G12D or G12V mutations in conjunction with an anti-KRAS vaccine to participants with metastatic solid cancers that contain KRAS G12D or G12V mutations. Eligibility: -Participants must be/have:
Design:
|
||||||||||||||
Study Type ICMJE | Interventional | ||||||||||||||
Study Phase ICMJE | Phase 1 | ||||||||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||||||||
Condition ICMJE |
|
||||||||||||||
Intervention ICMJE |
|
||||||||||||||
Study Arms ICMJE | Experimental: 1/ KRAS TCR + vaccine
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + KRAS TCR-Transduced PBL + high-dose aldesleukin + vaccine (Day 0, weeks 4 and 8 and at week 12 (if no progression)
Interventions:
|
||||||||||||||
Publications * | Not Provided | ||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||||||||
Recruitment Information | |||||||||||||||
Recruitment Status ICMJE | Recruiting | ||||||||||||||
Estimated Enrollment ICMJE |
210 | ||||||||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||||||||
Estimated Study Completion Date ICMJE | June 15, 2033 | ||||||||||||||
Estimated Primary Completion Date | June 15, 2031 (Final data collection date for primary outcome measure) | ||||||||||||||
Eligibility Criteria ICMJE |
Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and for 4 months after the last dose of combined chemotherapy. We also will recommend men with female partners of childbearing potential to ask female partners to be on highly effective birth control (hormonal, intrauterine device (IUD), surgical sterilization). NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. NOTE: Certain malignancies may secrete hormones that produce false positive pregnancy tests. Serial blood testing (e.g. HCG measurements) and/ or ultrasound may be performed for clarification.
NOTE: Participants 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.
EXCLUSION CRITERIA:
|
||||||||||||||
Sex/Gender ICMJE |
|
||||||||||||||
Ages ICMJE | 18 Years to 72 Years (Adult, Older Adult) | ||||||||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||||||||
Contacts ICMJE |
|
||||||||||||||
Listed Location Countries ICMJE | United States | ||||||||||||||
Removed Location Countries | |||||||||||||||
Administrative Information | |||||||||||||||
NCT Number ICMJE | NCT06253520 | ||||||||||||||
Other Study ID Numbers ICMJE | 10001662 001662-C |
||||||||||||||
Has Data Monitoring Committee | Not Provided | ||||||||||||||
U.S. FDA-regulated Product |
|
||||||||||||||
IPD Sharing Statement ICMJE |
|
||||||||||||||
Current Responsible Party | National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) | ||||||||||||||
Original Responsible Party | Same as current | ||||||||||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||||||||
Collaborators ICMJE | Not Provided | ||||||||||||||
Investigators ICMJE |
|
||||||||||||||
PRS Account | National Institutes of Health Clinical Center (CC) | ||||||||||||||
Verification Date | February 20, 2024 | ||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |