Background:
A new cancer therapy involves taking white blood cells from a person, growing them in the
lab, genetically modifying them, then giving them back to the person. This therapy is
called gene transfer using anti-KRAS G12V mTCR cells.
Objective:
To see if anti-KRAS G12 V mTCR cells are safe and can shrink tumors.
Eligibility:
Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface
of tumors.
Design:
In another protocol, participants will:
Be screened
Have cells harvested and grown
Have leukapheresis
In this protocol, participants will have the procedures below.
Participants will be admitted to the hospital.
Over 5 days, participants will get 2 chemotherapy medicines as an infusion via catheter
in the upper chest.
A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter.
For up to 3 days, participants will get a drug to make the cells active.
A day after getting the cells, participants will get a drug to increase their white blood
cell count. This will be a shot or injection under the skin.
Participants will recover in the hospital for 1-2 weeks. They will have lab and blood
tests.
Participants will take an antibiotic for at least 6 months.
Participants will have visits every few months for 2 years, and then as determined by
their doctor.
Visits will be 1-2 days. They will include lab tests, imaging studies, and physical exam.
Some visits may include leukapheresis or blood drawn.
Participants will have blood collected over several years.
Additional locations may be listed on ClinicalTrials.gov for NCT03190941.
Locations matching your search criteria
United States
Maryland
Bethesda
National Institutes of Health Clinical CenterStatus: Active
Contact: NCI/Surgery Branch Recruitment Center
Phone: 866-820-4505
Background:
- We generated an HLA-A*11:01-restricted murine T-cell receptor (mTCR) that
specifically recognizes the G12V-mutated variant of KRAS (and other RAS family
genes), expressed by many human cancers and constructed a single retroviral vector
that contains alpha and beta chains that confer recognition of this antigen when
transduced into PBL.
- In co-cultures with HLA-A*11:01+ target cells expressing this mutated oncogene, mTCR
transduced T cells lyse target cells and secrete IFN-gamma with high specificity.
Objectives:
Primary objectives:
- Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12V
mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2;
aldesleukin).
- Phase II: Determine if anti-KRAS G12V mTCR-transduced PBL can mediate the regression
of tumors harboring the RAS G12V mutation.
Eligibility:
Patients must be/have:
- Age greater than or equal to 18 years and less than or equal to 72 years
- HLA-A*11:01 positive
- Metastatic or unresectable RAS G12V-expressing cancer which has progressed after
standard therapy (if available).
Patients may not have:
-Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide or
fludarabine.
Design:
- This is a Phase I/II, single center study of PBL transduced with anti-KRAS G12V mTCR
in HLA-A*11:01 positive patients with advanced solid tumors expressing G12V mutated
RAS.
- PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3)
and aldesleukin in order to stimulate T-cell growth.
- Transduction is initiated by exposure of these cells to retroviral vector
supernatant containing replication-incompetent virus encoding the anti-KRAS G12V
mTCR.
- All patients will receive a non-myeloablative, lymphodepleting preparative regimen
of cyclophosphamide and fludarabine.
- On day 0, patients will receive their PBL transduced with the anti-KRAS G12V mTCR
and will then begin high-dose aldesleukin.
- A complete evaluation of lesions will be conducted approximately 6 weeks (+/- 2
weeks) after treatment.
- The study will be conducted using a phase I/II Simon minimax design, with two
separate
cohorts for the Phase II component: Cohort 2a, patients with RAS G12V pancreatic
cancer, and Cohort 2b, patients with RAS G12V non-pancreatic cancer.
-A total of up to 110 patients may be required; approximately 24 patients in the phase I
portion of the study and 86 (41, plus an allowance of up to 2 non-evaluable per phase II
cohort) patients in the phase II portion of the study.
Lead OrganizationNational Cancer Institute
Principal InvestigatorJames Chung-Yin Yang