Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials.
Jeremy L Davis, Marc R Theoret, Zhili Zheng...
https://pubmed.ncbi.nlm.nih.gov/21138872Actively Recruiting
Phase 1
Phase 2
Age: 18Years - 72Years
All Genders
ID03190941
A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients
Led by National Cancer Institute (NCI) · Updated on 2026-05-29
110
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are investigating a new gene therapy using anti-KRAS G12V mTCR cells to treat adults with advanced cancers that carry the KRAS G12V mutation. This Phase I/II study aims to assess the safety of this therapy and whether it can shrink tumors in patients positive for HLA-A*11:01, including those with pancreatic and non-pancreatic cancers. The therapy involves genetically modifying patients' own white blood cells to target cancer cells specifically. Participants receive a preparative lymphodepleting regimen with cyclophosphamide and fludarabine over several days before getting the anti-KRAS G12V mTCR cells infused back into their bloodstream. Following cell infusion, patients receive high-dose aldesleukin to activate the cells. This process includes hospitalization for chemotherapy infusions, cell infusion, and recovery lasting 1 to 2 weeks. Additionally, participants take an antibiotic for at least 6 months to support treatment. Throughout the study, participants undergo regular follow-up visits for up to two years or longer as needed, including physical exams, lab tests, imaging studies, and blood collections. Researchers monitor tumor response at 6 and 12 weeks post-treatment and regularly assess for treatment-related side effects. Blood samples may be collected over several years to study long-term effects. The study involves close clinical monitoring to evaluate both safety and tumor regression.
CONDITIONS
Brief Title
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients
Who Can Participate
Age: 18Years - 72Years
All Genders
Eligibility Criteria
You may qualify if you...
- Age between 18 and 72 years
- HLA-A*11:01 positive as confirmed by testing
- Measurable metastatic or unresectable cancer expressing G12V mutated KRAS or similar RAS mutations
- Previously received or declined standard systemic therapy for advanced cancer
- Clinical performance status of ECOG 0 or 1
- Willingness to use birth control during and after treatment
- Women of child-bearing potential must agree to pregnancy testing before treatment
- Seronegative for HIV, hepatitis B antigen, and hepatitis C antibody (with additional testing if needed)
- Adequate blood counts (ANC >1000/mm3, WBC ≥2500/mm3, platelets ≥80,000/mm3, hemoglobin >8.0 g/dL)
- Liver function tests within specified limits (ALT/AST ≤5x ULN, bilirubin ≤2.0 mg/dL or ≤3.0 mg/dL with Gilbert's Syndrome)
- Kidney function with eGFR >60 mL/min or 6-24 hour creatinine clearance >60 mL/min
- Completed prior systemic therapy at enrollment
- Ability to understand and sign informed consent
- Willingness to sign durable power of attorney
- Co-enrollment on protocol 03C0277
You will not qualify if you...
- Large volume pulmonary irradiation
- Pregnant or breastfeeding women
- Concurrent systemic steroid therapy
- Active systemic infections or major uncontrolled medical illnesses
- Primary immunodeficiency disorders
- Concurrent opportunistic infections
- History of severe allergic reactions to cyclophosphamide, fludarabine, or aldesleukin
- History of coronary revascularization or ischemic heart symptoms
- Reduced heart function if clinically indicated (LVEF ≤45%)
- Reduced lung function if clinically indicated (FEV1 ≤50% or DLCO <60%)
- Receiving other investigational agents
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Run-in Period
Duration - 5 to 7 days
Participants receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine before cell infusion.
Daily visits for up to 7 days
Treatment
Duration - Up to 4 days
Participants receive an infusion of PBL transduced with anti-KRAS G12V mTCR followed by high-dose aldesleukin therapy.
1 infusion visit and up to 9 aldesleukin doses over 3 days with frequent monitoring
Follow-up
Duration - Approximately 6 weeks (+/- 2 weeks)
Participants undergo evaluations of tumor response and safety monitoring after treatment.
1 follow-up visit approximately 6 weeks after treatment
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Loading map...
Research Team
N
NCI SB Immunotherapy Recruitment Center
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here
Published Research Related To This Trial
Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors.
Qiong J Wang, Zhiya Yu, Kayla Griffith...
https://pubmed.ncbi.nlm.nih.gov/26701267Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations.
S I Abrams, S N Khleif, E S Bergmann-Leitner...
https://pubmed.ncbi.nlm.nih.gov/9514698