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

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-Kirsten rat sarcoma virus (KRAS) Glycine(G) to Aspartic Acid(D) substitution at codon 12(G12D) murine T-cell receptor (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 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.

Conditions

• Gastrointestinal Cancer
• Pancreatic Cancer
• Gastric Cancer
• Colon Cancer
• Rectal Cancer

Interventions

DRUG

Cyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days intravenous (IV) in 250 mL 5% Dextrose in water (D5W) infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

DRUG

Fludarabine

Days -7 to -3: Fludarabine 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.

DRUG

Aldesleukin

Aldesleukin 720,000 IU/kg intravenous (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).

BIOLOGICAL

anti-Kirsten rat sarcoma virus (KRAS) Glycine(G) to Aspartic Acid(D) substitution at codon 12 peripheral blood lymphocytes (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).

DIAGNOSTIC_TEST

EKG

Baseline within 14 days prior to preparative regimen

DIAGNOSTIC_TEST

CT

Within 6 weeks and post treatment follow-up

DIAGNOSTIC_TEST

MRI

Within 6 weeks and post treatment follow-up

DIAGNOSTIC_TEST

PET

Within 6 weeks and post treatment follow-up

DIAGNOSTIC_TEST

Chest x-ray

Baseline within 14 days prior to preparative regimen

OTHER

Photography

Within 6 weeks and post treatment follow-up

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• James C Yang, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

72 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-05-16

Primary Completion

2022-08-23

Completion

2022-08-23

FDA Drug

Yes

Countries

• United States

Study Locations