RecruitingPhase 1Phase 2NCT03190941

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

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

Sponsor

National Cancer Institute (NCI)

Enrollment

110 participants

Start Date

Sep 21, 2017

Study Type

INTERVENTIONAL

Conditions

Pancreatic Cancer Gastric Cancer Colon Cancer Rectal Cancer Gastrointestinal Cancer

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 72 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a treatment where a patient's own immune cells are genetically engineered to recognize and attack cancer cells that carry a specific genetic mutation called KRAS G12V — a mutation found in some lung, colon, and pancreatic cancers — in people whose cancer has spread and cannot be removed by surgery. **You may be eligible if...** - Your cancer has been confirmed to carry the KRAS G12V mutation (or a closely related mutation in NRAS or HRAS) - Your cancer is measurable and has spread or cannot be surgically removed - You have a specific immune system tissue type called HLA-A*11:01 (determined by a blood test) - You are in reasonably good health - Standard treatments have not worked **You may NOT be eligible if...** - Your tumor does not carry the required genetic mutation - You do not have the specific immune tissue type required - You have active autoimmune conditions or serious infections - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGCyclophosphamide

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.

DRUGFludarabine

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

BIOLOGICALAnti-KRAS G12V mTCR PBL

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

DRUGAldesleukin

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).