RecruitingPhase 1Phase 2NCT03745326

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D 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 G12D Variant of Mutated RAS in HLA-A*11:01 Patients


Sponsor

National Cancer Institute (NCI)

Enrollment

70 participants

Start Date

May 16, 2019

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 72 Years

Plain Language Summary

Simplified for easier understanding

This trial is studying a type of personalized cell therapy — where a patient's own immune cells are re-engineered to attack a specific mutation found in several cancers — for people with advanced solid tumors carrying the KRAS G12D mutation. **You may be eligible if...** - You have an advanced or metastatic solid cancer (such as pancreatic, colorectal, or lung cancer) that has the KRAS G12D mutation (confirmed by a lab test) - You carry the HLA-A*11:01 tissue type (a specific immune marker, confirmed by blood test) - Your cancer has not responded to standard treatments - You are otherwise in acceptable health and 18 years or older **You may NOT be eligible if...** - Your tumor does not have the KRAS G12D (or equivalent RAS) mutation - You do not have the HLA-A*11:01 tissue type - You have autoimmune disease or are on immunosuppressive therapy - You are pregnant or breastfeeding - You have active brain metastases or severe organ problems 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/m\^2/day IVPB daily over 30 minutes for 5 days.

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).

BIOLOGICALanti-KRAS G12D 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).


Locations(1)

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

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NCT03745326


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