Background:
A new cancer therapy takes white blood cells from a person, grows them in a lab,
genetically changes them, then gives them back to the person. Researchers think this may
help attack tumors in people with certain cancers. It is called gene transfer using
anti-KRAS G12D mTCR cells.
Objective:
To see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink.
Eligibility:
Adults ages 18-72 who have cancer with a molecule on the tumors that can be recognized by
the study cells
Design:
Participants will be screened with medical history, physical exam, scans, photography,
and heart, lung, and lab tests.
An intravenous (IV) catheter will be placed in a large vein in the chest.
Participants will have leukapheresis. Blood will be removed through a needle in an arm. A
machine will divide the blood and collect white blood cells. The rest of the blood will
be returned to the participant through a needle in the other arm.
A few weeks later, participants will have a hospital stay. They will:
- Get 2 chemotherapy medicines by IV over 5 days.
- Get the changed cells through the catheter. Get up to 9 doses of a medicine to help
the cells. They may get a shot to stimulate blood cells.
- Recover in the hospital for up to 3 weeks. They will provide blood samples.
Participants will take an antibiotic for at least 6 months.
Participants will have several follow-up visits over 2 years. They will repeat most of
the screening tests and may have leukapheresis.
Participants blood will be collected for several years.
Additional locations may be listed on ClinicalTrials.gov for NCT03745326.
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-A11:01-restricted murine T-cell receptor (mTCR) that
specifically recognizes the G12D-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-A11:01+ 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 G12D
mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2;
aldesleukin).
- Phase II: Determine if anti-KRAS G12D mTCR-transduced PBL can mediate the regression
of tumors harboring the RAS G12D mutation.
Eligibility:
- Patients must be/have:
- Age greater than or equal to 18 years and less than or eqaul to 72 years
- HLA-A*11:01 positive
- Metastatic or unresectable RAS G12D-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 G12D mTCR
in HLA-A*11:01 positive patients with advanced solid tumors expressing G12D 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 G12D
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 G12D mTCR
and will then begin high-dose aldesleukin.
- A complete evaluation of lesions will be conducted approximately 6 weeks (plus-minus
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 G12D
pancreatic cancer, and Cohort 2b, patients with RAS G12D non-pancreatic cancer.
- A total of up to 70 patients may be required; approximately 24 patients in the Phase
I portion of the study and 46 (21, 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